异常细胞间通讯在白血病中作用机制研究
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摘要
细胞通讯是维持细胞生存和功能的基础,其异常与疾病密切相关,在经典单向信号传递机制的的基础上,发现并初步阐明了反向信号传递现象,其研究成为生命科学研究热点之一。mM-CSF是巨噬细胞集落刺激因子(M-CSF)的一种选择性剪接产物,为膜结合型细胞因子,我们前期的研究证实了它具有并置性和粘附分子样作用,与其受体结合后可能传递双向信号。本论文在我室多年研究的基础上,对mM-CSF介导的反向信号及其传递机制进行了探讨。
构建了野生型和突变型mM-CSF的pTARGET真核表达载体以及MSCV-PGK-GFP逆转录病毒载体,经DNA测序证实后分别转染、感染Namalwa细胞,筛选获得了稳定表达细胞株；用MSCV-PGK-GFP转染HEK293细胞,获得阳性表达细胞。采用RT-PCR和Western blot方法证实上述细胞构建成功。
以稳定表达野生型mM-CSF的Namalwa细胞株以及瞬时表达mM-CSF的HEK293细胞为模型,研究mM-CSF介导的反向信号传递。可溶性受体作用后可引起胞内分子量约为40kD的蛋白酪氨酸磷酸化水平显著升高；蛋白芯片结果显示多种蛋白激酶磷酸化水平发生变化；Western blot方法进一步证实ERK、Akt在可溶性受体作用后磷酸化水平升高,提示mM-CSF可以介导反向信号,并且ERK、Akt信号途径参与该反向信号传递。
以稳定表达截短突变型(胞内截短30个氨基酸残基)以及胞内三点突变型(Ser226、Ser235和Thr246均突变为Ala) mM-CSF的Namalwa细胞株以及瞬时表达二者的HEK293细胞为模型,用同样的方法研究mM-CSF胞内区在反向信号传递中的作用。可溶性受体作用后无上述蛋白激酶磷酸化水平的改变,提示mM-CSF胞内区,特别是胞内区的Ser226、Ser235和Thr246在反向信号传递中起关键作用。
为进一步探讨mM-CSF介导反向信号的传递机制,以稳定表达胞内区单点突变型(Ser226突变为Ala)和双点突变型(Ser235和Thr246均突变为Ala) mM-CSF的Namalwa细胞株为模型,研究胞内区三位点各自在反向信号传递中的作用异同。初步结果显示,Ser226在反向信号传递中起重要作用。
综上所述,本文深入研究了mM-CSF介导的反向信号及其传递机制,证实了mM-CSF可以介导反向信号。首次证明了ERK、Akt信号途径参与该反向信号传递；mM-CSF的胞内区特别是Ser226、Ser235和Thr246在介导反向信号传递中其关键作用,且作用方式存在差异,Ser226的作用更显著。
RNA编辑是一种重要的转录后修饰过程,它通过对核苷酸的修饰改变遗传信息。目前发现主要的编辑形式是由编码双链RNA特异性腺苷脱氨酶(ADAR, adenosine deaminase that act on RNA)修饰的腺嘌吟核苷(adenosine)到次黄嘌呤核苷(insosine)的改变,即A-to-I转换。编码双链RNA特异性腺苷脱氨酶-1(ADAR1)基因是ADAR基因家族中的一员,通过选择性剪接产生多种亚型,主要包括干扰素诱导的分子量为150kDa蛋白(p150)和组成性表达的分子量为110kDa的蛋白(p110),二者在病理生理过程中,发挥着重要作用。目前,在白血病中,他们的表达和意义还不是很清楚。我们采用实时定量PCR和western blot方法,从基因水平和蛋白水平证明了ADAR1亚型在儿童急性白血病患者的骨髓单个核细胞中广泛表达,样本来自于116例初诊的儿童急性白血病患者,20例复发患者,16例治疗后达到完全缓解的患者,26例随访的患者以及20例相对正常对照患者。结果发现,ADAR1亚型p110在初诊的急性淋巴细胞白血病患者中的表达显著高于对照,尤其高表达于B淋巴细胞性急性白血病患者；然而p150却只有轻度的增高。另外,p110在治疗后达到缓解的患者中表达下降。值得注意的是,p110和p150的表达与临床预后危险度因素相关,二者高表达于标危组,低表达于高危组。我们进一步根据预后相关的临床指标进行分组,研究二者在不同组别的表达与预后相关因素的关系。ADAR1亚型不同的表达特点,提示它们在儿童白血病中可能发挥着不同的作用,为白血病治疗寻找潜在靶标奠定理论基础。
Cellular communication is the foundation of cellular society exists and running. The abnormal intercellular communication is closely related to human diseases. Though classical mechanism of intercellular communication, based on one-directional signal transduction, has been deeply investigated and the research of reverse signal has become one of the hot points in life science. The membrane form of macrophage colony-stimulating factor (mM-CSF) is an alternative splicing variant of this cytokine. As the proteolytic cleavage sites used to release the secreted isoforms have been spliced out, mM-CSF is stably expressed at the cell surface. Our previous research showed that mM-CSF could play juxtacrine and adhesion molecule-like roles. It could transfer two-directional signal after binding its recepteors. Basing on our previous studies on mM-CSF, we try to explore the roles of mM-CSF in reverse signal and the mechanisms of transmission mediated by mM-CSF.
In this study, we construct mM-CSF and mM-CSF mutation eukaryotic expression vector pTARGET and retroviruses carrier MSCV-PGK-GFP. Stable and transient transfectant clones expressing mM-CSF and mM-CSF mutation (Namalwa-M and Namalwa-M mutation) were obtained. Namalwa-M and Namalwa-M mutation were verified by RT-PCR and Western blot methods.
Using stably transfected clones (Namalwa-M) and transient transfectant clones (HEK293-M), we studied the reverse signal by mM-CSF. The tyrosine phosphorylation level of several proteins with the molecular masses of approximately 40kD was increased by sM-CSFR stimulation. Furthermore, using phospory-kinase arrays, we demonstrated that the phosphorylation level of several protein kinases was changed after sM-CSFR stimulation. The result suggested that ERK/MAPK and Akt signal pathway were involved in this reverse signal by Western blot methods.
Using stably transfected Namalwa-M-30 (brachytmema mutation of 30 amino acide located in the intracellular region of mM-CSF) and Namalwa-M 10 (Ser226、Ser235 and Thr246 mutated to Ala) and transient transfectant HEK293-M-30 and HEK293-M10 clones, we studied the role of the intracellular region of mM-CSF in reverse signal. The result suggested demonstrated that there was no reverse signal in above-mentioned cells by the same methods. We demonstrated that the intracellular region of mM-CSF, especially Ser226、Ser2235 and Thr246 located in the intracellular region of mM-CSF play important roles in reverse signal.
To further explore the mechanisms of reverse signal mediated by mM-CSF, using stably transfected clones which was expressing one site (Ser226 mutated to Ala) or two sites (Ser235 and Thr246 mutated to Ala) mutation on serine or threonine residues located in the intracellular region of mM-CSF, we studied the different role of serine or threonine residues located in the intracellular region of mM-CSF in reverse signal. The initial result suggested that Ser226 play the important role.
In conclusions, we deeply explored the roles of mM-CSF in reverse signal and the mechanisms of transmission mediated by mM-CSF. We demonstrated that mM-CSF can transmit reverse signal and first proved that ERK/MAPK and Akt signal pathway were involved in this reverse signal. We first proved by experiments that the intracellular region of mM-CSF play important roles and Ser226、Ser235 and Thr246 located in the intracellular region of mM-CSF play the different role in reverse signal, especially the important role of the Ser226.
RNA editing is an important posttranscriptional process, through which RNA base sequences are altered. Several different forms of RNA editing, catalyzed by two classes of enzymes, occur in humans and the predominant RNA editing in mammals is adenosine-to-inosine (A-I) editing, which is catalyzed by adenosine deaminases acting on RNAs (ADARs). The posttranscriptional RNA editing by the type 1 adenosine deaminase acting on RNAs (ADAR1), expressed as constitutively expressed p110 and IFN-inducible p150 isoforms, is important for both physiological and pathological processes. Their expression and significance in leukemias remain unknown.116 newly diagnosed pediatric acute leukemia patients,20 relapsed patients,16 patients achieving complete remission,26 follow-up patients and 20 control cases were included for the expression of ADAR1 isoforms by real-time PCR and Western blot. The results showed that significant high expression of p110 was detected in leukemias, especially in B-ALL, whereas a slight increase of p150 could be observed. Furthermore, the decrease of p110 expression was observed in B-ALL patients achieving complete remission. Moreover, among prognostic risk groups in ALL, the highest expressions of p110 and p150 were detected in standard-risk group, whereas their lowest expressions were in high-risk group. This observation was further confirmed in comparisons between good and poor prognostic groups based on prognostic related clinical features. These results demonstrated that ADAR1 isoforms showed different expression patterns, suggesting that they might play different roles in pediatric leukemias. Our results will help us for the better understanding of RNA editing, exploring the potential target for the treatment, and making prognostic evaluation in childhood leukemias.
构建了野生型和突变型mM-CSF的pTARGET真核表达载体以及MSCV-PGK-GFP逆转录病毒载体,经DNA测序证实后分别转染、感染Namalwa细胞,筛选获得了稳定表达细胞株；用MSCV-PGK-GFP转染HEK293细胞,获得阳性表达细胞。采用RT-PCR和Western blot方法证实上述细胞构建成功。
以稳定表达野生型mM-CSF的Namalwa细胞株以及瞬时表达mM-CSF的HEK293细胞为模型,研究mM-CSF介导的反向信号传递。可溶性受体作用后可引起胞内分子量约为40kD的蛋白酪氨酸磷酸化水平显著升高；蛋白芯片结果显示多种蛋白激酶磷酸化水平发生变化；Western blot方法进一步证实ERK、Akt在可溶性受体作用后磷酸化水平升高,提示mM-CSF可以介导反向信号,并且ERK、Akt信号途径参与该反向信号传递。
以稳定表达截短突变型(胞内截短30个氨基酸残基)以及胞内三点突变型(Ser226、Ser235和Thr246均突变为Ala) mM-CSF的Namalwa细胞株以及瞬时表达二者的HEK293细胞为模型,用同样的方法研究mM-CSF胞内区在反向信号传递中的作用。可溶性受体作用后无上述蛋白激酶磷酸化水平的改变,提示mM-CSF胞内区,特别是胞内区的Ser226、Ser235和Thr246在反向信号传递中起关键作用。
为进一步探讨mM-CSF介导反向信号的传递机制,以稳定表达胞内区单点突变型(Ser226突变为Ala)和双点突变型(Ser235和Thr246均突变为Ala) mM-CSF的Namalwa细胞株为模型,研究胞内区三位点各自在反向信号传递中的作用异同。初步结果显示,Ser226在反向信号传递中起重要作用。
综上所述,本文深入研究了mM-CSF介导的反向信号及其传递机制,证实了mM-CSF可以介导反向信号。首次证明了ERK、Akt信号途径参与该反向信号传递；mM-CSF的胞内区特别是Ser226、Ser235和Thr246在介导反向信号传递中其关键作用,且作用方式存在差异,Ser226的作用更显著。
RNA编辑是一种重要的转录后修饰过程,它通过对核苷酸的修饰改变遗传信息。目前发现主要的编辑形式是由编码双链RNA特异性腺苷脱氨酶(ADAR, adenosine deaminase that act on RNA)修饰的腺嘌吟核苷(adenosine)到次黄嘌呤核苷(insosine)的改变,即A-to-I转换。编码双链RNA特异性腺苷脱氨酶-1(ADAR1)基因是ADAR基因家族中的一员,通过选择性剪接产生多种亚型,主要包括干扰素诱导的分子量为150kDa蛋白(p150)和组成性表达的分子量为110kDa的蛋白(p110),二者在病理生理过程中,发挥着重要作用。目前,在白血病中,他们的表达和意义还不是很清楚。我们采用实时定量PCR和western blot方法,从基因水平和蛋白水平证明了ADAR1亚型在儿童急性白血病患者的骨髓单个核细胞中广泛表达,样本来自于116例初诊的儿童急性白血病患者,20例复发患者,16例治疗后达到完全缓解的患者,26例随访的患者以及20例相对正常对照患者。结果发现,ADAR1亚型p110在初诊的急性淋巴细胞白血病患者中的表达显著高于对照,尤其高表达于B淋巴细胞性急性白血病患者；然而p150却只有轻度的增高。另外,p110在治疗后达到缓解的患者中表达下降。值得注意的是,p110和p150的表达与临床预后危险度因素相关,二者高表达于标危组,低表达于高危组。我们进一步根据预后相关的临床指标进行分组,研究二者在不同组别的表达与预后相关因素的关系。ADAR1亚型不同的表达特点,提示它们在儿童白血病中可能发挥着不同的作用,为白血病治疗寻找潜在靶标奠定理论基础。
Cellular communication is the foundation of cellular society exists and running. The abnormal intercellular communication is closely related to human diseases. Though classical mechanism of intercellular communication, based on one-directional signal transduction, has been deeply investigated and the research of reverse signal has become one of the hot points in life science. The membrane form of macrophage colony-stimulating factor (mM-CSF) is an alternative splicing variant of this cytokine. As the proteolytic cleavage sites used to release the secreted isoforms have been spliced out, mM-CSF is stably expressed at the cell surface. Our previous research showed that mM-CSF could play juxtacrine and adhesion molecule-like roles. It could transfer two-directional signal after binding its recepteors. Basing on our previous studies on mM-CSF, we try to explore the roles of mM-CSF in reverse signal and the mechanisms of transmission mediated by mM-CSF.
In this study, we construct mM-CSF and mM-CSF mutation eukaryotic expression vector pTARGET and retroviruses carrier MSCV-PGK-GFP. Stable and transient transfectant clones expressing mM-CSF and mM-CSF mutation (Namalwa-M and Namalwa-M mutation) were obtained. Namalwa-M and Namalwa-M mutation were verified by RT-PCR and Western blot methods.
Using stably transfected clones (Namalwa-M) and transient transfectant clones (HEK293-M), we studied the reverse signal by mM-CSF. The tyrosine phosphorylation level of several proteins with the molecular masses of approximately 40kD was increased by sM-CSFR stimulation. Furthermore, using phospory-kinase arrays, we demonstrated that the phosphorylation level of several protein kinases was changed after sM-CSFR stimulation. The result suggested that ERK/MAPK and Akt signal pathway were involved in this reverse signal by Western blot methods.
Using stably transfected Namalwa-M-30 (brachytmema mutation of 30 amino acide located in the intracellular region of mM-CSF) and Namalwa-M 10 (Ser226、Ser235 and Thr246 mutated to Ala) and transient transfectant HEK293-M-30 and HEK293-M10 clones, we studied the role of the intracellular region of mM-CSF in reverse signal. The result suggested demonstrated that there was no reverse signal in above-mentioned cells by the same methods. We demonstrated that the intracellular region of mM-CSF, especially Ser226、Ser2235 and Thr246 located in the intracellular region of mM-CSF play important roles in reverse signal.
To further explore the mechanisms of reverse signal mediated by mM-CSF, using stably transfected clones which was expressing one site (Ser226 mutated to Ala) or two sites (Ser235 and Thr246 mutated to Ala) mutation on serine or threonine residues located in the intracellular region of mM-CSF, we studied the different role of serine or threonine residues located in the intracellular region of mM-CSF in reverse signal. The initial result suggested that Ser226 play the important role.
In conclusions, we deeply explored the roles of mM-CSF in reverse signal and the mechanisms of transmission mediated by mM-CSF. We demonstrated that mM-CSF can transmit reverse signal and first proved that ERK/MAPK and Akt signal pathway were involved in this reverse signal. We first proved by experiments that the intracellular region of mM-CSF play important roles and Ser226、Ser235 and Thr246 located in the intracellular region of mM-CSF play the different role in reverse signal, especially the important role of the Ser226.
RNA editing is an important posttranscriptional process, through which RNA base sequences are altered. Several different forms of RNA editing, catalyzed by two classes of enzymes, occur in humans and the predominant RNA editing in mammals is adenosine-to-inosine (A-I) editing, which is catalyzed by adenosine deaminases acting on RNAs (ADARs). The posttranscriptional RNA editing by the type 1 adenosine deaminase acting on RNAs (ADAR1), expressed as constitutively expressed p110 and IFN-inducible p150 isoforms, is important for both physiological and pathological processes. Their expression and significance in leukemias remain unknown.116 newly diagnosed pediatric acute leukemia patients,20 relapsed patients,16 patients achieving complete remission,26 follow-up patients and 20 control cases were included for the expression of ADAR1 isoforms by real-time PCR and Western blot. The results showed that significant high expression of p110 was detected in leukemias, especially in B-ALL, whereas a slight increase of p150 could be observed. Furthermore, the decrease of p110 expression was observed in B-ALL patients achieving complete remission. Moreover, among prognostic risk groups in ALL, the highest expressions of p110 and p150 were detected in standard-risk group, whereas their lowest expressions were in high-risk group. This observation was further confirmed in comparisons between good and poor prognostic groups based on prognostic related clinical features. These results demonstrated that ADAR1 isoforms showed different expression patterns, suggesting that they might play different roles in pediatric leukemias. Our results will help us for the better understanding of RNA editing, exploring the potential target for the treatment, and making prognostic evaluation in childhood leukemias.
引文
1 Himanen JP, Nikolov DB. Eph receptors and ephrins. Int J Biochem Cell Biol, 2003,35:130-134.
2 Aggarwal BB. Signaling pathways of the TNF superfamily:a double-edged sword. Nat Rev Immunol,2003,3:745-756.
3 Budagian V, Bulanova E, Orinska Z, Pohl T, Borden EC. Reverse Signaling through Membrane-bound Interleukin-15. J Biol Chem,2004,279:42192-42201.
4 Smith CA, Farrah T, Goodwin RG. The TNF receptor superfamily of cellular and viral proteins:activation, costimulation and death. Cell,1994,76:959-962.
5 Kawasaki ES, Ladner MB, Wang AM. Molecular cloning of a complementary DNA encoding human macrophage-specific colony-stimulating factor (CSF-1). Science, 1985,230:291-296.
6 Scholl SM, Pallud C, Beuvon F, Hacene K, Stanley ER, Rohrschneider L, et al. Anti-colony stimulating factor-1 antibody staining in primary breast adenocarcinomas correlate with marked inflammatory cell infiltrates and prognosis. J Natl Cancer Inst,1994,86:120.
7 Tamimi RM, Brugge JS, Freedman ML, Miron A, Iglehart JD, Colditz GA, Hankinson SE. Circulating colony stimulating factor-1 and breast cancer risk. Cancer Res,2008,68: 18-21.
8 Suzuki M, Kobayashi H, Ohwada M, Terao T, Sato I. Macrophage colony-stimulating factor as a marker for malignant germ cell tumors of the ovary. Gynecol Oncol, 1998,68:35-37.
9 Suzuki M, Tamura N, Kobayashi H, Ohwada M, Terao T, Sato I. Clinical significance of combined use of macrophage colonystimulating factor and squamous cell carcinoma antigen as a selective diagnostic marker for squamous cell carcinoma arising in mature cystic teratoma of the ovary. Gynecol Oncol,2000,77: 405-409.
10 Toy EP, Chambers JT, Kacinski BM. The activated macrophage colony-stimulating factor (CSF-1) receptor as a predictor of poor outcome in advanced epithelial ovarian carcinoma. Gynecol Oncol,2001,80:194.
11 Mroczko B, Groblewska M, Wereszczynska-Siemiatkowska U, Okulczyk B, Kedra B, Laszewicz W, et al. Serum macrophagecolony stimulating factor levels in colorectal cancer patients correlate with lymph node metastasis and poor prognosis. Clin Chim Acta,2007,380:208-212.
12 Mroczko B, Szmitkowski M, Okulczyk B. Granulocyte-colony stimulating factor (G-CSF) and macrophage colony stimulating factor (M-CSF) in colorectal cancer patients. Clin Chem Lab Med,2002,40:351-355.
13 Groblewska M, Mroczko B, Wereszczynska-Siemiatkowska U, Mysliwiec P, Kedra B, Szmitkowski M. Serum levels of granulocyte colony-stimulating factor (G-CSF) and macrophage colony-stimulating factor (M-CSF) in pancreatic cancer patients. Clin Chem Lab Med,2007,45:30-34.
14杨文清,吴克复.巨噬细胞集落刺激因子及受体与非造血系统发育和疾病的发生.国外医学临床生物化学与检验分册,1999,20：331.
15杨文清,吴克复,宋乃国.巨噬细胞集落刺激因子在动脉粥样硬化和慢性肾功能衰竭中的作用.国外医学临床生物化学与检验分册,1998,19：215.
16 Cerretti DP, Wignall J, Anderson D. Human macrophage-colony stimulating factor:alternative RNA and protein processing from a single gene. Mol Immunol, 1988,25:761-770.
17 Shadle PJ, Aldwin L, Nitecki DE, Koths K. Human macrophage colony-stimulating factor heterogeneity results from alternative mRNA splicing, differential glycosylation, and proteolytic processing. J Cell Biochem,1989,40:91-107.
18 Das SK, Stanley ER. Structure-function studies of a colony stimulating factor (CSF-1). J Biol Chem,1982,257:13679-13684.
19 Sherr CJ, Rettenmier CW, Sacca R, Roussel MF, Look AT, Stanley ER. The c-fms proto-oncogene product is related to the receptor for the mononuclear phagocyte growth factor, CSF-1. Cell,1985,41:665-676.
20 Zheng GG, Wu KF, Geng YQ. Expression of membrane-bound M-CSF in Hodgkin's disease and other hematologic malignancies. Leukemia & Lymphoma,1999,32: 339.
21 Rao Q, Zheng GG, Li G, Lin YM, Wu KF. Membrane-bound macrophage colony-stimulating factor mediated auto-juxtacrine downregulates matrix metalloproteinase-9 release on J6-1 leukemic cell. Exp Biol Med,2004,229: 946-953.
22 Zheng G, Rao Q, Wu K, He Z, Geng YQ. Membrane-bound macrophage colony-stimulating factor and its receptor play adhesion molecule-like roles in leukemic cells. Leuk Res,2000,24:375-383.
23 Holland SJ. Bidirectional signalling through the EPH family receptor Nuk and its transmembrane ligands. Nature,1996,383:722-725.
24 Pocsik E, Duda E, Wallach D. Phosphorylation of the 26 kDa TNF precursor in monocytic cells and in transfected HeLa cells. J Inflamm,1995,45:152-160.
25 David W, LITCHFIELD. Protein kinase CK2:structure, regulation and role in cellular decisions of life and death. Biochem J,2003,369:1-15.
26 Sanlo S, Reddy H, Meggio F, et al. Selectivity 4,5,6,7-tetrabromobenzotriazole, an ATP site-directed inhibitor protein kinase CK2. FEBS Lett,2001,496:44-48.
27 Corbin J D, Sugden PH, West L, et al. Studies on the properties and mode of action of the purified regulatory subunit of bovine heart adenosine 3',5'-monop hosphate-dependent protein kinase. J Biol Chem,1978,253:3997-4003.
28 Ollivier V, Parry G, Cobb R R, et al. Elevated cyclic AMP inhibit s NF-κB-mediated transcription in human monocytic cells and endothelial cells. J Biol Chem,1996,271:20828-20835.
29 Neumann M, Grieshammer T, Chuvpilo S, et al. RelA/p65 is a molecular target for the mmunosuppressive action of protein kinase A. EMBOJ,1995,14:1991-2004.
30 Peng HY, Cheng YW, Lee SD, et al. Glutamate-mediated spinal reflex potentiation involves ERK 1/2 phosphorylation in anesthetized rats. Neuropharmacology,2008, 54:686-698.
1 Rice KL, Hormaeche I, Licht JD. Epigenetic regulation of normal and malignant hematopoiesis. Oncogene,2007,26:6697-6714.
2 Bass BL. RNA editing by adenosine deaminases that act on RNA. Annu Rev Biochem,2002,71:817-846.
3 Maas S, Rich A, Nishikura K. A-to-I RNA editing:recent news and residual mysteries. J Biol Chem,2003,278:1391-1394.
4 Valente L, Nishikura K. ADAR gene family and A-to-I RNA editing:diverse roles in posttranscriptional gene regulation. Prog Nucleic Acid Res Mol Biol,2005,79: 299-338.
5 Morse DP, Aruscavage PJ, Bass BL. RNA hairpins in noncoding regions of human brain and Caenorhabditis elegans mRNA are edited by adenosine deaminases that act on RNA. Proc Natl Acad Sci USA,2002,99:7906-7911.
6 Wang Q, Khilan J, Gadue P, Nishikura K. Requirement of the RNA editing deaminase ADAR1 gene for embryonic erythropoiesis. Science,2000,290: 1765-1776.
7 Hartner JC, Schmittwolf C, Kispert A, Miiller AM, Higuchi M, Seeburg PH. Liver disintegration in the mouse embryo caused by deficiency in the RNA-editing enzyme ADAR1. J Biol Chem,2004,279:4894-4902.
8 Hartner JC, Walkley CR, Lu J, Orkin SH. ADAR1 is essential for the maintenance of hematopoiesis and suppression of interferon signaling. Nat Immunol,2009,10: 109-115.
9 XuFeng R, Boyer MJ, Shen H, Li Y, Yu H, Gao Y, et al. ADAR1 is required for hematopoietic progenitor cell survival via RNA editing. Proc Natl Acad Sci USA,2009,106:17763-17768.
10 Yang JH, Luo X, Nie Y, Su Y, Zhao Q, Kabir K, et al. Widespread inosine-containing mRNA in lymphocytes regulated by ADAR1 in response to inflammation. Immunology,2003,109:15-23.
11 Yang JH, Nie Y, Zhao Q, Su Y, Pypaert M, Su H, et al. Intracellular localization of differentially regulated RNA-specific adenosine deaminase isoforms in inflammation. J Biol Chem,2003,278:45833-45842.
12 Poison AG, Bass BL, Casey JL. RNA editing of hepatitis delta virus antigenome by dsRNA-adenosine deaminase. Nature,1996,380:454-456.
13 Kawakubo K and Samuel CE. Human RNA-specific adenosine deaminase (ADAR1) gene specifies transcripts that initiate from a constitutively active alternative promoter. Gene,2000,258:165-172.
14 Paz N, Levanon EY, Amariglio N, Heimberger AB, Ram Z, Constantini S, et al. Altered adenosine-to-inosine RNA editing in human cancer. Genome Res,2007, 17:1586-1595.
15 George CX, Samuel CE. Human RNA-specific adenosine deaminase ADAR1 transcripts possess alternative exon 1 structures that initiate from different promoters, one constitutively active and the other interferon inducible. Proc Natl Acad Sci USA,1999,96:4621-4626.
16 Strehblow A, Hallegger M, Jantsch MF. Nucleocytoplasmic distribution of human RNA editing enzyme ADAR1 is modulated by double stranded RNA-binding domains, a leucine-rich export signal, and a putative dimerization domain. Mol Biol Cell,2002,13:3822-3835.
17 Poulsen H, Nilsson J, Damgaard CK, Egebjerg J, Kjems J. CRM1 mediates the export of ADAR1 through a nuclear export signal within the Z-DNA binding domain. Mol Cell Biol,2001,21:7862-7871.
18 Livak, KJ and Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods,2001, 25:402-408.
19 Keller W, Wolf J, Gerber A. Editing of messenger RNA precursors and of tRNAs by adenosine to inosine conversion. FEBS Lett,1999; 452:71-76.
20 Mehler MF. Epigenetic principles and mechanisms underlying nervous system functions in health and disease. Prog Neurobiol, 2008,86:305-341.
21 Wang Q, Miyakoda M, Yang W, Khillan J, Stachura DL, Weiss MJ, Nishikura K. Stress-induced apoptosis associated with null mutation of ADAR1 RNA editing deaminase gene. J Biol Chem,2004,279:4952-4961.
22 Cenci C, Barzotti R, Galeano F, Corbelli S, Rota R, Massimi L, et al. Down-regulation of RNA editing in pediatric astrocytomas:ADAR2 editing activity inhibits cell migration and proliferation. J Biol Chem,2008,283: 7251-7260.
23 Beghini A, Ripamonti CB, Peterlongo P, Roversi G, Cairoli R, Morra E, et al. RNA hyperediting and alternative splicing of hematopoietic cell phosphatase (PTPN6) gene in acute myeloid leukemia. Hum Mol Genet,2000,9:2297-2304.
24 Chong JH, Zheng GG, Zhu XF, Guo Y, Wang L, Ma CH, et al. Abnormal expression of P2X family receptors in Chinese pediatric acute leukemias. Biochem Biophys Res Commun,2010,391:498-504.
25 Tendier CL, Burton JD, Jatte J, Danielpour D, Charley M, McCoy JP, et al. Abnormal Cytokine Expression in Sezary and Adult T-Cell Leukemia Cells Correlates with the Functional Diversity between These T-Cell Malignancies. Cancer Res,1994,54:4430-4435.
26 Pui CH, Robison LL, Look AT. Acute lymphoblastic leukaemia. Lancet,2008, 371:1030-1043.
27 Hafiz MG, Rahman MM, Mannan MA. Serum lactate dehydrogenase as prognostic marker of childhood acute lymphoblastic leukemia. Mymensingh Med J,2008,17: 169-173.
28 Wang Y, Samuel CE. Adenosine deaminase ADAR1 increases gene expression at the translational level by decreasing protein kinase PKR-dependent eIF-2a phosphorylation. J Mol Biol,2009,393:777-787.
1 Tuck DP, Cerretti DP, Hand A, et al. Human macrophage colony-stimulating factor is expressed at and shed from the cell surface. Blood,1994,84:2182-2188.
2 Cerretti DP, Wignall J, Anderson D, et al. Membrane bound forms of human macrophage colony stimulating factor (M-CSF, CSF-1). Prog Clin Biol Res, 1990,352:63-70.
3 Cerretti DP, Wignall J, Anderson D, et al. Human macrophage-colony stimulating factor:alternative RNA and protein processing from a single gene. Mol Immunol, 1988,25:761-70.
4 Kimura F, Suzu S, Nakamura Y, et al. Structural analysis of proteoglycan macrophage colony-stimulating factor. J Biol Chem,1994,269:19751-19756.
5 Kawasaki ES, Ladner MB, Wang AM, et al. Molecular cloning of a complementary DNA encoding human macrophage-specific colony-stimulating factor (CSF-1). Science,1985,230:291-296.
6 Ladner MB, Martin GA, Noble JA, et al. Human CSF-1:Gene structure and alternative splicing of mRNA precursors. EMBOJ,1987,6:2693-2698.
7 Wong GG, Temple PA, Leary AC, et al. Human CSF-1:Molecular cloning and expression of 4 kb cDNA encoding the human urinary protein. Science,1987,235: 1504-1508.
8 Flxe P, Praloran V. M-CSF:hematopoiesis growth factor or inflammatory cytokine? Cytokine,1998,10:32-37.
9 Tang S, Du X, Chen G, et al. The expression and effects of isoforms of macrophage colony stimulating factor in human leukemic cell lines. Chin J Pathol,2000,29: 111-114.
10 Pettenati MJ, Le B, Lemons RS, et al. Assignment of CSF-I to 5 q33.1:Evidence for clustering of genes regulating hematopoiesis and for their involvement in the deletion of the long arm of chromosome 5 in myeloid disorders. Proc Natl Acad Sci USA,1987,84:2970-2974.
11 Kawasaki ES, Ladner MB, Wang AM, et al. Molecular cloning of a complementary DNA encoding human macrophage-specific colony-stimulating factor (CSF-1). Science,1985,230:291-296.
12 Ladner MB, Martin GA, Noble JA, et al. Human CSF-1:gene structure and alternative splicing of mRNA precursors. EMBOJ,1987,6:2693-2698.
13 Pampfer S, Tabibzadeh S, Chuan FC, et al. Expression of colony-stimulating factor-1 (CSF-1) messenger RNA in human endometrial glands during the menstrual cycle:molecular cloning of a novel transcript that predicts a cell surface form of CSF-1. Mol Endocrinol,1991,5:1931-1938.
14 Rettenmier CW. Biosynthesis of macrophage colony-stimulating factor (CSF-1): differential processing of CSF-1 precursors suggests alternative mechanisms for stimulating CSF-1 receptors. Curr Top Microbiol Immunol,1989,149:129-141.
15 Rettenmier CW, Roussel MF, Ashmun RA, et al. Synthesis of membrane-bound colony-stimulating factor 1 (CSF-1) and downmodulation of CSF-1 receptors in NIH 3T3 cells transformed by cotransfection of the human CSF-1 and c-fms (CSF-1 receptor) genes. Mol Cell Biol,1987,7:2378-2387.
16 Rettenmier CW and Roussel MF. Differential processing of colony-stimulating factor 1 precursors encoded by two human cDNAs. Mol Cell Biol,1988,8: 5026-5034.
17 Manos MM. Expression and processing of a recombinant human macrophage colony-stimulating factor in mouse cells. Mol Cell Bio,1988,18:5035-5039.
18 Jeremiah Stein, Gary V. Borzillo and Carl W. Rettenmier Direct Stimulation of Cells Expressing Receptors for Macrophage Colony-Stimulating Factor (CSF-1) by a Plasma Membrane-Bound Precursor of Human CSF-1. Blood,1990,76:1308-1314.
19 Dubreuil P, Torres H, Courcoul MA, et al. c-fms expression is a molecular marker of human acute myeloid leukemias. Blood,1988,72:1081-1085.
20 Parwaresch MR, Kreipe H, Felgner J, et al. M-CSF and M-CSF-receptor gene expression in acute myelomonocytic leukemias. Leuk Res,1990,14:27-37.
21 Baiocchi G, Kavanagh JJ, Talpaz M, et al. Expression of the macrophage colony-stimulating factor and its receptor in gynecologic malignancies. Cancer, 1991,67:990-996.
22 Lowenberg B and Touw IP. Hematopoietic growth factor and their receptors in acute leukemia. Blood,1993,81:281-292.
23 Dainik N. Surface membrane-associated regulation of cell assembly, differentiation and growth. Blood,1991,78:264-276.
24 Caligaris-Cappio F, Bergui L, Schena M, et al. Cell-cell and cell-matrix adhesion structures may influence the growth pattern of chronic lymphoid malignancies. Leukemia,1989,3:167-169.
25 Anklesaria P, Teixido J, Laiho M, et al. Cell-cell adhesion mediated by binding of membrane-anchored transforming growth factor alpha to epidermal growth factor receptors promotes cell proliferation. Proc Natl Acad Sci USA,1990,87: 3289-3293.
26 Wu KF, Zhong YQ and Qi SL. Establishment of myeloid,monocytic leukemic cell lines and studies of their cell biological properties. Acta Genetic Sinica,1980,7: 136.
27 Wu KF, Rao Q, Zheng GG, et al. Enhancement of J6-1 human leukemic cell proliferation by cell-cell contact:role of an M-CSF-like membrane-associated growth factor MAF-J6-1. Leuk Res,1994,18:843-849.
28 Li G, Song YH, Wu KF, et al. Clone and expression of mutant M-CSF and its receptor from human leukemic cell line J6-1. Leuk Res,2002,26:377-382.
29 Wu KF, Rao Q, Zheng GG, et al. Enhancement of J6-1 human leukemic cell proliferation by membrane-bound M-CSF through a cell-cell contact mechanism II: Role of an M-CSF receptor-like membrane protein. Leuk Res,1998,22:55-60.
30 Rao Q, Zheng GG, Li G, et al. Membrane-bound macrophage colony-stimulating factor mediated auto-juxtacrine down regulates matrix metalloproteinase-9 release on J6-1 leukemic cell. Exp Biol Med,2004,229:946-953.
31 Zheng G, Rao Q, Wu K, et al. Membrane-bound macrophage colony-stimulating factor and its receptor play adhesion molecule-like roles in leukemic cells. Leuk Res,2000,24:375-383.
32 Jadus MR, Irwin M, Irwin MR, et al. Macrophages can recognize and kill tumor cells bearing the membrane isoform of macrophage colony-stimulating factor. Blood,1996,87:5232-5241.
33 Jadus MR, Williams CC, Avina MD, et al. Macrophages kill T9 Glioma tumor cells bearing the membrane isoform of macrophage colony stimulating factor through a phagocytosis-dependent pathway. J Immunol,1998,160:361-368.
34 Williams CC, Trinh H, Tran TV, et al. Membrane macrophage colony-stimulating factor on MADB106 breast cancer cells does not activate cytotoxic macrophages but immunizes rats against breast cancer. Mol Ther,2001,3:216-224.
35 Dan Q, Sanchez R, Delgado C, et al. Non-immunogenic murine hepatocellular carcinoma hepal-6 cells expressing the membrane form of macrophage colony stimulating factor are rejected in vivo and lead to CD8+T-cell immunity against the parental tumor. Mol Ther,2001,4:427-437.
36 Sanchez R, Williams C, Daza JL, et al. T9 glioma cells expressing membrane-macrophage colony stimulating factor produce CD4+T cell-associated protective immunity against T9 intracranial gliomas and systemic immunity against different syngeneic gliomas. Cell Immunol,2002,215:1-11.
37 Jadus MR, Chen Y, Boldaji MT, et al. Human U251MG glioma cells expressing the membrane form of macrophage colony-stimulating factor (mM-CSF) are killed by human monocytes in vitro and are rejected within immunodeficient mice via paraptosis that is associated with increased expression of three different heat shock proteins. Cancer Gene Therapy,2003,10:411-420.
38 Yao GQ, Sun B, Hammond EE, et al. The cell-surface form of colony-stimulating factor-1 is regulated by osteotropic agents and supports formation of multinucleated osteoclast-like cells. J Biol Chem,1998,273:4119-4128.
39 Fan X, Fan D, Gewant H, et al. Increasing membrane-bound M-CSF does not enhance opgl-driven osteoclasto genesis from marrow cells. Am J Physiol,2001, 280:103-111.
40 Yao GQ, Sun BH, Weir EC, et al. A role for cell-surface CSF-1 in osteoblast-mediated osteoclastogenesis. Calcif Tissue Int,2002,70:339-346.
41 Yao G, Wu J, Sun B, et al. The cell surface form of colony-stimulating factor-1 is biologically active in bone in vivo. Endocrinology,2003,144:3677-3682.
42 Horiuchi K, Miyamoto T, Takaishi H, et al. Cell surface colony-stimulating factor 1 can be cleaved by TNF-a converting enzyme or endocytosed in a clathrin-dependent manner. J Immunol,2007,179:6715-6724.
43 Dai X, Zong X, Sylvestre V, et al. Incomplete restoration of colony-stimulating factor 1 (CSF-1) function in CSF-1-deficient Csflop/Csflop mice by transgenic expression of cell surface CSF-1. Blood,2004,103:1114-1123.
44 Ovadia S, Insogna K and Yao GQ. The cell-surface isoform of colony stimulating factor 1 (CSF1) restores but does not completely normalize fecundity in CSF1-deficient mice. Biol Reprod,2006,74:331-336.
45 Tesch GH, Schwarting A, Kinoshita K, et al. Monocyte chemoattractant protein-1 promotes macrophagemediated tubular injury, but not glomerular injury, in nephrotoxic serum nephritis. J Clin Invest,1999,103:73-80.
46 Pixley FJ and Stanley ER. CSF-1 regulation of the wandering macrophage: complexity in action. Trends Cell Biol,2004,14:628-638.
47 Stanley ER, Berg KL, Einstein DB, et al. Biology and action of colony-stimulating factor-1. Mol Rep Dev,1997,46:4-10.
48 Price LK, Choi HU, Rosenberg L, et al. The predominant form of secreted colony stimulating factor-1 is a proteoglycan. J Biol Chem,1992,267:2190-2219.
49 Price L. Biosynthetic studies of membrane associated and secreted cell CSF-1.1992. Doctoral dissertation, Albert Einstein College of Medicine of Yeshiva University, New York, p.150.
50 Bartocci A, Mastrogiannis DS, Migliorati G, et al. Macrophages specifically regulate the concentration of their own growth factor in the circulation. Proc Natl Acad Sci USA,1987,84:6179-6183.
51 Cecchini MG, Dominguez MG, Mocci S, et al. Role of colony stimulating factor-1 in the establishment and regulation of tissue macrophages during postnatal development of the mouse. Development,1994,120:1357-1372.
52 Dai XM, Zong XH, Sylvestre V, et al. Incomplete restoration of colony-stimulating factor 1 (CSF-1) function in CSF-1-deficient Csflop/Csflop mice by transgenic expression of cell surface CSF-1. Blood,2004,103:1114-1123.
53 Stanley ER. Colony-stimulating factor (CSF) radioimmunoassay:detection of a CSF subclass stimulating macrophage production. Proc Natl Acad Sci USA,1979,76: 2969-2973.
54 Nandi S, Akhter MP, Seifert MF, et al. Developmental and functional significance of the CSF-1 proteoglycan chondroitin sulfate chain. Blood,2006,107:786-795.
55 Jang MH, Herber DM, Jiang X, et al. Kelley distinct in vivo roles of colony-stimulating factor-1 isoforms in renal inflammation. J Immunol,2006,177: 4055-4063.
1 Angela Gallpo and Silvia Galardi. A-to-I RNA editing and cancer. RNA Biology, 2008,5(3):135-139.
2 Weier HU, George CX, Grenlich KM, et al. The interferon-inducible, double-stranded RNA-specific adenosine deaminase gene (DSRAD) maps to human chromosome 1q21.1-21.2. Genonucs,1995,30(2):372-375.
3 Kim U, Wang Y, Sanford T. et al. Molecular cloning of cDNA for double-stranded RNA adenosine deaminase, a candidate enzyme for nuclear RNA editing. Proc Natl Acad Sci USA,1994,91(24):11457-11461.
4 O'Connell MA, Krause S, Higuchi M. et al. Cloning of cDNAs encoding mammalian double-stranded RNA-specific adenosine deaminase. Mol Cell Biol,1995,15(3): 1389-1397.
5 Liu Y, George CX, Patterson JB, et al. Functionally distinct double-stranded RNA-binding domains associated with alternative splice site variants of the interferon-inducible double-stranded RNA-specific adenosine deaminase. J Biol Chem,1997,272(7):4419-4428.
6 Patterson JB, Samuel CE. Expression and regulation by interferon of a double-stranded-RNA-specific adenosine deaminase from human cells:evidence for two forms of the deaminase. Mol Cell Biol,1995,15(10):5376-5388.
7 George CX, Samuel CE. Human RNA-specie adenosine deaminase ADAR1 transcripts possess alternative exon 1 structures that initiate from different promoters, one constitutively active and the other interferon inducible. Proc Natl Acad Sci USA,1999,96(8):4621-4626.
8 Kawakubo K. Samuel CE. Human RNA-specific adenosine deaminase (ADAR1) gene specifies transcripts that initiate from a constitutively active alternative promoter. Gene,2000,258(1-2):165-172.
9 Yang JH, Nie Y, Zhao Q, et al. Intracellular localization of differentially regulated RNA-specific adenosine deaminase isoforms in inflammation. J Biol Chem,2003, 278(46):45833-45842.
10 Macbeth MR, Schubert HL, Vandemark AP, Lingam AT, Hill CP, Bass BL. Inositol hexakisphosphate is bound in the ADAR2 core and required for RNA editing. Science,2005,309:1534-1539.
11 Wagner RW, Yoo C, Wrabetz L, Kamholz J, Buchhalter J, Hassan NF, Khalili K, Kim SU, Perussia B, McMorris FA and Nishikura K. Double-stranded RNA unwinding and modifying activity is detected ubiquitously in primary tissues and cell lines. Mol Cell Biol,1990,10:5586-5590.
12 Liu Y, George CX, Patterson JB and Samuel CE. Functionally distinct double-stranded RNA-binding domains associated with alternative splice site variants of the interferon-inducible double-stranded RNA-specific adenosine deaminase. J Biol Chem.1997,272:4419-4428.
13 Gerber A, O'Connell MA and Keller W. Two forms of human double-stranded RNA-specific editase 1 (hRED1) generated by the insertion of an Alu cassette. RNA,1997,3:453-463.
14 Higuchi M. Maas S, Single FN, et al. Point mutation in an AMPA receptor gene rescues lethality in mice deficient in the RNA-editing enzyme ADAR2. Nature, 2000,406(6791):78-81.
15 Chen CX, Cho DS, Wang Q, et al. A third member of the RNA-specific adenosine deaminase gene family, ADAR3, contains both single-and double-stranded RNA binding domains. RNA,2000,6:755-767.
16 Melcher T, Maas S, Herb A, Sprengel R, Higuchi M and Seeburg PH. RED2, a brain-specific member of the RNA-specific adenosine deaminase family. J Biol Chem,1996,271:31795-31798.
17 Chilibeck KA, WuT, Liang C, Schellenberg MJ, Gesner EM, Lynch JM and MacMillan AM. FRET analysis of in vivo dimerization by RNA-editing enzymes. J Bio Chem,2006,281:16530-16535.
18 Gallo A, Keegan LP, Ring GM and O'Connell MA. An ADAR that edits transcripts encoding ion channel subunits functions as a dimer. EMBO J,2003, 22:3421-3430.
19 Poulsen H, Jorgensen R, Heding A, Nielsen FC, Bonven B and Egebjerg J. Dimerization of ADAR2 is mediated by the double-stranded RNA binding domain. RNA,2006,12:1350-1360.
20 Cho DS, Yang W, Lee JT, Shiekhattar R, Murray JM and Nishikura K. Requirement of dimerization for RNA editing activity of adenosine deaminases acting on RNA. J Biol Chem,2003,278:17093-17102.
21 Cenci C, Barzotti R, Galeano F, Corbelli S, Rota R, Massimi L, Di Rocco C, O'Connell MA, Gallo A. Down regulation of RNA editing in pediatric astrocytomas:ADAR2 editing activity inhibits cell migration and proliferation. J Biol Chem,2008,283:7251-7260.
22 Gerber AP, Keller W. An adenosine deaminase that generates inosine at the wobble position of tRNAs. Science,1999,286:1146-1149.
23 Gerber A, Grosjean H, Melcher T, Keller W. Tadlp, a yeast tRNA-specific adenosine deaminase, is related to the mammalian pre-mRNA editing enzymes ADAR1 and ADAR2. EMBOJ,1998,17:4780-4789.
24 Maas S, Gerber AP, Rich A. Identification and characterization of a human tRNA-specific adenosine deaminase related to the ADAR family of pre-mRNA editing enzymes. Proc Natl Acad Sci USA,1999,96:8895-8900.
25 Keegan LP, Gerber AP, Brindle J, Leemans R, Gallo A, et al. The properties of a tRNA-specific adenosine deaminase from Drosophila melanogaster support an evolutionary link between pre-mRNA editing and tRNA modification. Mol Cell Biol,2000,20:825-833.
26 Morse DP, Aruscavage P J, Bass BL, et al. RNA hairpins in noncoding regions of human brain and Caenorhabditis elegans mRNA are edited by adenosine deam-inases that act on RNA. Proc Natl Acad Sci USA,2002,99(12):7906-7911.
27 Mendell JT. miRiad roles for the miR-17-92 cluster in development and disease. Cell 2008;133:217-22.
28 Luciano DJ, Mirsky H, Vendetti NJ, Maas S. RNA editing of a miRNA precursor. RNA,2004,10:1174-1177.
29 Blow MJ, Grocock RJ, van Dongen S, Enright AJ, Dicks E, Futreal PA, Wooster R, Stratton MR. RNA editing of human microRNAs. Genome Biol,2006,7: 27.
30 Pfeffer S, Sewer A, Lagos-Quintana M, Sheridan R, Sander C, Grasser FA, van Dyk LF, Ho CK,Shuman S, Chien M, Russo JJ, Ju J, Randall G, Lindenbach BD, Rice CM, Simon V, Ho DD,Zavolan M, Tuschl T. Identification of microRNAs of the herpesvirus family. Nat Methods,2005,2:269-276.
31 Kawahara Y, Zinshteyn B, Sethupathy P, lizasa H, Hatzigeorgiou AG, Nishikura K. Redirection of silencing targets by adenosine-to-inosine editing of miRNAs. Science,2007,315:1137-1140.
32 Kawahara Y, Zinshteyn B, Chendrimada TP, Shiekhattar R, Nishikura K. RNA editing of the microRNA-151 precursor blocks cleavage by the Dicer-TRBP complex. EMBO Rep,2007,8:763-769.
33 Seeburg PH. A-to-I editing:new and old sites, functions and speculations. Neuron, 2002,35(1):17-20.
34 Maas S, Rich A, Nishikura K, et al. A-to-I RNA editing:recent news and residual mysteries. J Biol Chem,2003,278(3):11391-1394.
35 Poison AG, Bass BL, Casey JL. RNA editing of hepatitis delta virus antigenome by dsRNA-adenosine deaminase. Nature,1996,380(6573):454-456.
36 Scadden AD. Smith CW. A ribonuclease specific for inosine-containing RNA:a potential role in antiviral defence? EMBOJ,1997,16(8):2140-2149.
37 Rabinovici R, Kabir K, Chen M. et al. ADAR1 is involved in the development of microvascular lung injury. Circ Res,2001,88(10):1066-1071.
38 Yang JH, Luo X, Nie Y, et al. Widespread inosine-containing mRNA in lymphocytes regulated by ADAR1 in response to inflammation. Immunology, 2003,109(1):15-23.
39 Herbert A. Wagner S, Nickerson JA. Induction of protein translation by ADAR1 within living cell nuclei is not dependent on RNA editing. Mol Cell,2002,10(5): 1235-1246.
40 Lund E, Dahlberg JE. Proofreading and aminoacylation of tRNAs before export from the nucleus. Science,1998,282(5396):2082-2085.
41 Pederson T, Politz JC. The nucleolus and the four ribonucleoproteins of translation. J Cell Biol,2000,148(6):1091-1096.
42 lborra FJ, Jackson DA, Cook PR. Coupled transcription and translation within nuclei of mammalian cells. Science,2001,293:1139-1142.
43 Maas S, Patt S, Schrey M, Rich A. Underediting of glutamate receptor GluR-B mRNA in malignant gliomas. Proc Natl Acad Sci USA,2001,98:14687-14692.
44 Rickert CH, Paulus W. Epidemiology of central nervous system tumors in childhood and adolescence based on the new WHO classification. Childs Nerv Syst,2001,17:503-511.
45 Cohen KJ, Broniscer A, Glod J. Pediatric glial tumors. Curr Treat Options Oncol, 2001,2:529-536.
46 Wang Q, Khilan J, Gadue P, et al. Requirement of the RNA editing deaminase ADARl gene for embryonic erythropoiesis. Science,2000,290(5497):17651776.
47 Wang Q, Miyakoda M, Yang W, et al. Stress-induced apoptosis associated with null mutation of ADAR1 RNA editing deaminase gene. J Biol Chem,2004,279(6): 4952-4961.
48 Hartner JC, Schimittwolf C, Kispert A, et al. Liver disintegration in the mouse embryo caused by deficiency in the RNA editing enzyme ADAR1. J Biol Chem, 2004,279(6):4894-4902.
49 Hartner JC, Walkley CR, Lu J, Orkin SH. ADARl is essential for the maintenance of hematopoiesis and suppression of interferon signaling. Nat Immunol,2009,10: 109-115.
50 Richard XuFeng, Matthew J, Boyer, Hongmei Shen, Yanxin Li, Hui Yu, Yindai Gao, Qiong Yang, Qingde Wang, and Tao Cheng. ADAR1 is required for hematopoietic progenitor cell survival via RNA editing. PNAS,2009,106 (42):17763-17768.
51 Beghini A, Ripamonti CB, Peterlongo P, Roversi G, Cairoli R, Morra E, et al. RNA hyperediting and alternative splicing of hematopoietic cell phosphatase (PTPN6) gene in acute myeloid leukemia. Hum Mol Genet,2000,9:2297-2304.
52 Paz N, Levanon EY, Amariglio N, Heimberger AB, Ram Z, Constantini S, et al. Altered adenosine-to-inosine RNA editing in human cancer. Genome Res, 2007,17:1586-1595.
53 Wang Q, Miyakoda M, Yang W, Khillan J, Stachura DL, Weiss MJ, Nishikura K. Stress-induced apoptosis associated with null mutation of ADAR1 RNA editing deaminase gene. J Biol Chem,2004,279:4952-4961.
54 Wang Y, Samuel CE. Adenosine deaminase ADARl increases gene expression at the translational level by decreasing protein kinase PKR-dependent eIF-2a phosphorylation. J Mol Biol,2009,393:777-787.
55 Zhang XJ, Gao M, Li M, et al. Identification of a locus for dyschromatosis symmetrica hereditaria at chromosome 1q11-1q21. J Invest Dermatol,2003, 120(5):776-780.
56 Miyamura Y, Suzuki T, Kono M, et al. Mutations of the RNA-specific adenosine deaminase gene (DSRAD) are involved in dyschromatosis symmetrica hereditaria. Am J Ham Genet,2003,73(3):693-699.
57 Liu Q, Liu WL, Jiang L, et al. Novel Mutations of the RNA-Specific Adenosine Deaminase Gene (DSRAD)in Chinese Families with Dyschromatosis Symmetrica Hereditaria. J Invest Dermatol,2004,122(4):896-899.
58 Furen Zhang, Hong Liu, Deke Jiang, Hongqing Tian, Changyuan Wang, Long Yu. Six novel mutations of the ADAR1 gene in Chinese patients with dyschromatosis symmetrica hereditaria Journal of Dermatological Science,2008, 50:109-114.
59 Ming Li, Lijia Yang, Chengrang Li, Cheng Jin, Meiling Lai, Guolong Zhang, Yan Hu, Jin ji, Zhirong Yao. Mutational spectrum of the ADAR1 gene in dyschromatosis symmetrica hereditaria. Arch Dermatol Res,2010,302:469-476.
2 Aggarwal BB. Signaling pathways of the TNF superfamily:a double-edged sword. Nat Rev Immunol,2003,3:745-756.
3 Budagian V, Bulanova E, Orinska Z, Pohl T, Borden EC. Reverse Signaling through Membrane-bound Interleukin-15. J Biol Chem,2004,279:42192-42201.
4 Smith CA, Farrah T, Goodwin RG. The TNF receptor superfamily of cellular and viral proteins:activation, costimulation and death. Cell,1994,76:959-962.
5 Kawasaki ES, Ladner MB, Wang AM. Molecular cloning of a complementary DNA encoding human macrophage-specific colony-stimulating factor (CSF-1). Science, 1985,230:291-296.
6 Scholl SM, Pallud C, Beuvon F, Hacene K, Stanley ER, Rohrschneider L, et al. Anti-colony stimulating factor-1 antibody staining in primary breast adenocarcinomas correlate with marked inflammatory cell infiltrates and prognosis. J Natl Cancer Inst,1994,86:120.
7 Tamimi RM, Brugge JS, Freedman ML, Miron A, Iglehart JD, Colditz GA, Hankinson SE. Circulating colony stimulating factor-1 and breast cancer risk. Cancer Res,2008,68: 18-21.
8 Suzuki M, Kobayashi H, Ohwada M, Terao T, Sato I. Macrophage colony-stimulating factor as a marker for malignant germ cell tumors of the ovary. Gynecol Oncol, 1998,68:35-37.
9 Suzuki M, Tamura N, Kobayashi H, Ohwada M, Terao T, Sato I. Clinical significance of combined use of macrophage colonystimulating factor and squamous cell carcinoma antigen as a selective diagnostic marker for squamous cell carcinoma arising in mature cystic teratoma of the ovary. Gynecol Oncol,2000,77: 405-409.
10 Toy EP, Chambers JT, Kacinski BM. The activated macrophage colony-stimulating factor (CSF-1) receptor as a predictor of poor outcome in advanced epithelial ovarian carcinoma. Gynecol Oncol,2001,80:194.
11 Mroczko B, Groblewska M, Wereszczynska-Siemiatkowska U, Okulczyk B, Kedra B, Laszewicz W, et al. Serum macrophagecolony stimulating factor levels in colorectal cancer patients correlate with lymph node metastasis and poor prognosis. Clin Chim Acta,2007,380:208-212.
12 Mroczko B, Szmitkowski M, Okulczyk B. Granulocyte-colony stimulating factor (G-CSF) and macrophage colony stimulating factor (M-CSF) in colorectal cancer patients. Clin Chem Lab Med,2002,40:351-355.
13 Groblewska M, Mroczko B, Wereszczynska-Siemiatkowska U, Mysliwiec P, Kedra B, Szmitkowski M. Serum levels of granulocyte colony-stimulating factor (G-CSF) and macrophage colony-stimulating factor (M-CSF) in pancreatic cancer patients. Clin Chem Lab Med,2007,45:30-34.
14杨文清,吴克复.巨噬细胞集落刺激因子及受体与非造血系统发育和疾病的发生.国外医学临床生物化学与检验分册,1999,20：331.
15杨文清,吴克复,宋乃国.巨噬细胞集落刺激因子在动脉粥样硬化和慢性肾功能衰竭中的作用.国外医学临床生物化学与检验分册,1998,19：215.
16 Cerretti DP, Wignall J, Anderson D. Human macrophage-colony stimulating factor:alternative RNA and protein processing from a single gene. Mol Immunol, 1988,25:761-770.
17 Shadle PJ, Aldwin L, Nitecki DE, Koths K. Human macrophage colony-stimulating factor heterogeneity results from alternative mRNA splicing, differential glycosylation, and proteolytic processing. J Cell Biochem,1989,40:91-107.
18 Das SK, Stanley ER. Structure-function studies of a colony stimulating factor (CSF-1). J Biol Chem,1982,257:13679-13684.
19 Sherr CJ, Rettenmier CW, Sacca R, Roussel MF, Look AT, Stanley ER. The c-fms proto-oncogene product is related to the receptor for the mononuclear phagocyte growth factor, CSF-1. Cell,1985,41:665-676.
20 Zheng GG, Wu KF, Geng YQ. Expression of membrane-bound M-CSF in Hodgkin's disease and other hematologic malignancies. Leukemia & Lymphoma,1999,32: 339.
21 Rao Q, Zheng GG, Li G, Lin YM, Wu KF. Membrane-bound macrophage colony-stimulating factor mediated auto-juxtacrine downregulates matrix metalloproteinase-9 release on J6-1 leukemic cell. Exp Biol Med,2004,229: 946-953.
22 Zheng G, Rao Q, Wu K, He Z, Geng YQ. Membrane-bound macrophage colony-stimulating factor and its receptor play adhesion molecule-like roles in leukemic cells. Leuk Res,2000,24:375-383.
23 Holland SJ. Bidirectional signalling through the EPH family receptor Nuk and its transmembrane ligands. Nature,1996,383:722-725.
24 Pocsik E, Duda E, Wallach D. Phosphorylation of the 26 kDa TNF precursor in monocytic cells and in transfected HeLa cells. J Inflamm,1995,45:152-160.
25 David W, LITCHFIELD. Protein kinase CK2:structure, regulation and role in cellular decisions of life and death. Biochem J,2003,369:1-15.
26 Sanlo S, Reddy H, Meggio F, et al. Selectivity 4,5,6,7-tetrabromobenzotriazole, an ATP site-directed inhibitor protein kinase CK2. FEBS Lett,2001,496:44-48.
27 Corbin J D, Sugden PH, West L, et al. Studies on the properties and mode of action of the purified regulatory subunit of bovine heart adenosine 3',5'-monop hosphate-dependent protein kinase. J Biol Chem,1978,253:3997-4003.
28 Ollivier V, Parry G, Cobb R R, et al. Elevated cyclic AMP inhibit s NF-κB-mediated transcription in human monocytic cells and endothelial cells. J Biol Chem,1996,271:20828-20835.
29 Neumann M, Grieshammer T, Chuvpilo S, et al. RelA/p65 is a molecular target for the mmunosuppressive action of protein kinase A. EMBOJ,1995,14:1991-2004.
30 Peng HY, Cheng YW, Lee SD, et al. Glutamate-mediated spinal reflex potentiation involves ERK 1/2 phosphorylation in anesthetized rats. Neuropharmacology,2008, 54:686-698.
1 Rice KL, Hormaeche I, Licht JD. Epigenetic regulation of normal and malignant hematopoiesis. Oncogene,2007,26:6697-6714.
2 Bass BL. RNA editing by adenosine deaminases that act on RNA. Annu Rev Biochem,2002,71:817-846.
3 Maas S, Rich A, Nishikura K. A-to-I RNA editing:recent news and residual mysteries. J Biol Chem,2003,278:1391-1394.
4 Valente L, Nishikura K. ADAR gene family and A-to-I RNA editing:diverse roles in posttranscriptional gene regulation. Prog Nucleic Acid Res Mol Biol,2005,79: 299-338.
5 Morse DP, Aruscavage PJ, Bass BL. RNA hairpins in noncoding regions of human brain and Caenorhabditis elegans mRNA are edited by adenosine deaminases that act on RNA. Proc Natl Acad Sci USA,2002,99:7906-7911.
6 Wang Q, Khilan J, Gadue P, Nishikura K. Requirement of the RNA editing deaminase ADAR1 gene for embryonic erythropoiesis. Science,2000,290: 1765-1776.
7 Hartner JC, Schmittwolf C, Kispert A, Miiller AM, Higuchi M, Seeburg PH. Liver disintegration in the mouse embryo caused by deficiency in the RNA-editing enzyme ADAR1. J Biol Chem,2004,279:4894-4902.
8 Hartner JC, Walkley CR, Lu J, Orkin SH. ADAR1 is essential for the maintenance of hematopoiesis and suppression of interferon signaling. Nat Immunol,2009,10: 109-115.
9 XuFeng R, Boyer MJ, Shen H, Li Y, Yu H, Gao Y, et al. ADAR1 is required for hematopoietic progenitor cell survival via RNA editing. Proc Natl Acad Sci USA,2009,106:17763-17768.
10 Yang JH, Luo X, Nie Y, Su Y, Zhao Q, Kabir K, et al. Widespread inosine-containing mRNA in lymphocytes regulated by ADAR1 in response to inflammation. Immunology,2003,109:15-23.
11 Yang JH, Nie Y, Zhao Q, Su Y, Pypaert M, Su H, et al. Intracellular localization of differentially regulated RNA-specific adenosine deaminase isoforms in inflammation. J Biol Chem,2003,278:45833-45842.
12 Poison AG, Bass BL, Casey JL. RNA editing of hepatitis delta virus antigenome by dsRNA-adenosine deaminase. Nature,1996,380:454-456.
13 Kawakubo K and Samuel CE. Human RNA-specific adenosine deaminase (ADAR1) gene specifies transcripts that initiate from a constitutively active alternative promoter. Gene,2000,258:165-172.
14 Paz N, Levanon EY, Amariglio N, Heimberger AB, Ram Z, Constantini S, et al. Altered adenosine-to-inosine RNA editing in human cancer. Genome Res,2007, 17:1586-1595.
15 George CX, Samuel CE. Human RNA-specific adenosine deaminase ADAR1 transcripts possess alternative exon 1 structures that initiate from different promoters, one constitutively active and the other interferon inducible. Proc Natl Acad Sci USA,1999,96:4621-4626.
16 Strehblow A, Hallegger M, Jantsch MF. Nucleocytoplasmic distribution of human RNA editing enzyme ADAR1 is modulated by double stranded RNA-binding domains, a leucine-rich export signal, and a putative dimerization domain. Mol Biol Cell,2002,13:3822-3835.
17 Poulsen H, Nilsson J, Damgaard CK, Egebjerg J, Kjems J. CRM1 mediates the export of ADAR1 through a nuclear export signal within the Z-DNA binding domain. Mol Cell Biol,2001,21:7862-7871.
18 Livak, KJ and Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods,2001, 25:402-408.
19 Keller W, Wolf J, Gerber A. Editing of messenger RNA precursors and of tRNAs by adenosine to inosine conversion. FEBS Lett,1999; 452:71-76.
20 Mehler MF. Epigenetic principles and mechanisms underlying nervous system functions in health and disease. Prog Neurobiol, 2008,86:305-341.
21 Wang Q, Miyakoda M, Yang W, Khillan J, Stachura DL, Weiss MJ, Nishikura K. Stress-induced apoptosis associated with null mutation of ADAR1 RNA editing deaminase gene. J Biol Chem,2004,279:4952-4961.
22 Cenci C, Barzotti R, Galeano F, Corbelli S, Rota R, Massimi L, et al. Down-regulation of RNA editing in pediatric astrocytomas:ADAR2 editing activity inhibits cell migration and proliferation. J Biol Chem,2008,283: 7251-7260.
23 Beghini A, Ripamonti CB, Peterlongo P, Roversi G, Cairoli R, Morra E, et al. RNA hyperediting and alternative splicing of hematopoietic cell phosphatase (PTPN6) gene in acute myeloid leukemia. Hum Mol Genet,2000,9:2297-2304.
24 Chong JH, Zheng GG, Zhu XF, Guo Y, Wang L, Ma CH, et al. Abnormal expression of P2X family receptors in Chinese pediatric acute leukemias. Biochem Biophys Res Commun,2010,391:498-504.
25 Tendier CL, Burton JD, Jatte J, Danielpour D, Charley M, McCoy JP, et al. Abnormal Cytokine Expression in Sezary and Adult T-Cell Leukemia Cells Correlates with the Functional Diversity between These T-Cell Malignancies. Cancer Res,1994,54:4430-4435.
26 Pui CH, Robison LL, Look AT. Acute lymphoblastic leukaemia. Lancet,2008, 371:1030-1043.
27 Hafiz MG, Rahman MM, Mannan MA. Serum lactate dehydrogenase as prognostic marker of childhood acute lymphoblastic leukemia. Mymensingh Med J,2008,17: 169-173.
28 Wang Y, Samuel CE. Adenosine deaminase ADAR1 increases gene expression at the translational level by decreasing protein kinase PKR-dependent eIF-2a phosphorylation. J Mol Biol,2009,393:777-787.
1 Tuck DP, Cerretti DP, Hand A, et al. Human macrophage colony-stimulating factor is expressed at and shed from the cell surface. Blood,1994,84:2182-2188.
2 Cerretti DP, Wignall J, Anderson D, et al. Membrane bound forms of human macrophage colony stimulating factor (M-CSF, CSF-1). Prog Clin Biol Res, 1990,352:63-70.
3 Cerretti DP, Wignall J, Anderson D, et al. Human macrophage-colony stimulating factor:alternative RNA and protein processing from a single gene. Mol Immunol, 1988,25:761-70.
4 Kimura F, Suzu S, Nakamura Y, et al. Structural analysis of proteoglycan macrophage colony-stimulating factor. J Biol Chem,1994,269:19751-19756.
5 Kawasaki ES, Ladner MB, Wang AM, et al. Molecular cloning of a complementary DNA encoding human macrophage-specific colony-stimulating factor (CSF-1). Science,1985,230:291-296.
6 Ladner MB, Martin GA, Noble JA, et al. Human CSF-1:Gene structure and alternative splicing of mRNA precursors. EMBOJ,1987,6:2693-2698.
7 Wong GG, Temple PA, Leary AC, et al. Human CSF-1:Molecular cloning and expression of 4 kb cDNA encoding the human urinary protein. Science,1987,235: 1504-1508.
8 Flxe P, Praloran V. M-CSF:hematopoiesis growth factor or inflammatory cytokine? Cytokine,1998,10:32-37.
9 Tang S, Du X, Chen G, et al. The expression and effects of isoforms of macrophage colony stimulating factor in human leukemic cell lines. Chin J Pathol,2000,29: 111-114.
10 Pettenati MJ, Le B, Lemons RS, et al. Assignment of CSF-I to 5 q33.1:Evidence for clustering of genes regulating hematopoiesis and for their involvement in the deletion of the long arm of chromosome 5 in myeloid disorders. Proc Natl Acad Sci USA,1987,84:2970-2974.
11 Kawasaki ES, Ladner MB, Wang AM, et al. Molecular cloning of a complementary DNA encoding human macrophage-specific colony-stimulating factor (CSF-1). Science,1985,230:291-296.
12 Ladner MB, Martin GA, Noble JA, et al. Human CSF-1:gene structure and alternative splicing of mRNA precursors. EMBOJ,1987,6:2693-2698.
13 Pampfer S, Tabibzadeh S, Chuan FC, et al. Expression of colony-stimulating factor-1 (CSF-1) messenger RNA in human endometrial glands during the menstrual cycle:molecular cloning of a novel transcript that predicts a cell surface form of CSF-1. Mol Endocrinol,1991,5:1931-1938.
14 Rettenmier CW. Biosynthesis of macrophage colony-stimulating factor (CSF-1): differential processing of CSF-1 precursors suggests alternative mechanisms for stimulating CSF-1 receptors. Curr Top Microbiol Immunol,1989,149:129-141.
15 Rettenmier CW, Roussel MF, Ashmun RA, et al. Synthesis of membrane-bound colony-stimulating factor 1 (CSF-1) and downmodulation of CSF-1 receptors in NIH 3T3 cells transformed by cotransfection of the human CSF-1 and c-fms (CSF-1 receptor) genes. Mol Cell Biol,1987,7:2378-2387.
16 Rettenmier CW and Roussel MF. Differential processing of colony-stimulating factor 1 precursors encoded by two human cDNAs. Mol Cell Biol,1988,8: 5026-5034.
17 Manos MM. Expression and processing of a recombinant human macrophage colony-stimulating factor in mouse cells. Mol Cell Bio,1988,18:5035-5039.
18 Jeremiah Stein, Gary V. Borzillo and Carl W. Rettenmier Direct Stimulation of Cells Expressing Receptors for Macrophage Colony-Stimulating Factor (CSF-1) by a Plasma Membrane-Bound Precursor of Human CSF-1. Blood,1990,76:1308-1314.
19 Dubreuil P, Torres H, Courcoul MA, et al. c-fms expression is a molecular marker of human acute myeloid leukemias. Blood,1988,72:1081-1085.
20 Parwaresch MR, Kreipe H, Felgner J, et al. M-CSF and M-CSF-receptor gene expression in acute myelomonocytic leukemias. Leuk Res,1990,14:27-37.
21 Baiocchi G, Kavanagh JJ, Talpaz M, et al. Expression of the macrophage colony-stimulating factor and its receptor in gynecologic malignancies. Cancer, 1991,67:990-996.
22 Lowenberg B and Touw IP. Hematopoietic growth factor and their receptors in acute leukemia. Blood,1993,81:281-292.
23 Dainik N. Surface membrane-associated regulation of cell assembly, differentiation and growth. Blood,1991,78:264-276.
24 Caligaris-Cappio F, Bergui L, Schena M, et al. Cell-cell and cell-matrix adhesion structures may influence the growth pattern of chronic lymphoid malignancies. Leukemia,1989,3:167-169.
25 Anklesaria P, Teixido J, Laiho M, et al. Cell-cell adhesion mediated by binding of membrane-anchored transforming growth factor alpha to epidermal growth factor receptors promotes cell proliferation. Proc Natl Acad Sci USA,1990,87: 3289-3293.
26 Wu KF, Zhong YQ and Qi SL. Establishment of myeloid,monocytic leukemic cell lines and studies of their cell biological properties. Acta Genetic Sinica,1980,7: 136.
27 Wu KF, Rao Q, Zheng GG, et al. Enhancement of J6-1 human leukemic cell proliferation by cell-cell contact:role of an M-CSF-like membrane-associated growth factor MAF-J6-1. Leuk Res,1994,18:843-849.
28 Li G, Song YH, Wu KF, et al. Clone and expression of mutant M-CSF and its receptor from human leukemic cell line J6-1. Leuk Res,2002,26:377-382.
29 Wu KF, Rao Q, Zheng GG, et al. Enhancement of J6-1 human leukemic cell proliferation by membrane-bound M-CSF through a cell-cell contact mechanism II: Role of an M-CSF receptor-like membrane protein. Leuk Res,1998,22:55-60.
30 Rao Q, Zheng GG, Li G, et al. Membrane-bound macrophage colony-stimulating factor mediated auto-juxtacrine down regulates matrix metalloproteinase-9 release on J6-1 leukemic cell. Exp Biol Med,2004,229:946-953.
31 Zheng G, Rao Q, Wu K, et al. Membrane-bound macrophage colony-stimulating factor and its receptor play adhesion molecule-like roles in leukemic cells. Leuk Res,2000,24:375-383.
32 Jadus MR, Irwin M, Irwin MR, et al. Macrophages can recognize and kill tumor cells bearing the membrane isoform of macrophage colony-stimulating factor. Blood,1996,87:5232-5241.
33 Jadus MR, Williams CC, Avina MD, et al. Macrophages kill T9 Glioma tumor cells bearing the membrane isoform of macrophage colony stimulating factor through a phagocytosis-dependent pathway. J Immunol,1998,160:361-368.
34 Williams CC, Trinh H, Tran TV, et al. Membrane macrophage colony-stimulating factor on MADB106 breast cancer cells does not activate cytotoxic macrophages but immunizes rats against breast cancer. Mol Ther,2001,3:216-224.
35 Dan Q, Sanchez R, Delgado C, et al. Non-immunogenic murine hepatocellular carcinoma hepal-6 cells expressing the membrane form of macrophage colony stimulating factor are rejected in vivo and lead to CD8+T-cell immunity against the parental tumor. Mol Ther,2001,4:427-437.
36 Sanchez R, Williams C, Daza JL, et al. T9 glioma cells expressing membrane-macrophage colony stimulating factor produce CD4+T cell-associated protective immunity against T9 intracranial gliomas and systemic immunity against different syngeneic gliomas. Cell Immunol,2002,215:1-11.
37 Jadus MR, Chen Y, Boldaji MT, et al. Human U251MG glioma cells expressing the membrane form of macrophage colony-stimulating factor (mM-CSF) are killed by human monocytes in vitro and are rejected within immunodeficient mice via paraptosis that is associated with increased expression of three different heat shock proteins. Cancer Gene Therapy,2003,10:411-420.
38 Yao GQ, Sun B, Hammond EE, et al. The cell-surface form of colony-stimulating factor-1 is regulated by osteotropic agents and supports formation of multinucleated osteoclast-like cells. J Biol Chem,1998,273:4119-4128.
39 Fan X, Fan D, Gewant H, et al. Increasing membrane-bound M-CSF does not enhance opgl-driven osteoclasto genesis from marrow cells. Am J Physiol,2001, 280:103-111.
40 Yao GQ, Sun BH, Weir EC, et al. A role for cell-surface CSF-1 in osteoblast-mediated osteoclastogenesis. Calcif Tissue Int,2002,70:339-346.
41 Yao G, Wu J, Sun B, et al. The cell surface form of colony-stimulating factor-1 is biologically active in bone in vivo. Endocrinology,2003,144:3677-3682.
42 Horiuchi K, Miyamoto T, Takaishi H, et al. Cell surface colony-stimulating factor 1 can be cleaved by TNF-a converting enzyme or endocytosed in a clathrin-dependent manner. J Immunol,2007,179:6715-6724.
43 Dai X, Zong X, Sylvestre V, et al. Incomplete restoration of colony-stimulating factor 1 (CSF-1) function in CSF-1-deficient Csflop/Csflop mice by transgenic expression of cell surface CSF-1. Blood,2004,103:1114-1123.
44 Ovadia S, Insogna K and Yao GQ. The cell-surface isoform of colony stimulating factor 1 (CSF1) restores but does not completely normalize fecundity in CSF1-deficient mice. Biol Reprod,2006,74:331-336.
45 Tesch GH, Schwarting A, Kinoshita K, et al. Monocyte chemoattractant protein-1 promotes macrophagemediated tubular injury, but not glomerular injury, in nephrotoxic serum nephritis. J Clin Invest,1999,103:73-80.
46 Pixley FJ and Stanley ER. CSF-1 regulation of the wandering macrophage: complexity in action. Trends Cell Biol,2004,14:628-638.
47 Stanley ER, Berg KL, Einstein DB, et al. Biology and action of colony-stimulating factor-1. Mol Rep Dev,1997,46:4-10.
48 Price LK, Choi HU, Rosenberg L, et al. The predominant form of secreted colony stimulating factor-1 is a proteoglycan. J Biol Chem,1992,267:2190-2219.
49 Price L. Biosynthetic studies of membrane associated and secreted cell CSF-1.1992. Doctoral dissertation, Albert Einstein College of Medicine of Yeshiva University, New York, p.150.
50 Bartocci A, Mastrogiannis DS, Migliorati G, et al. Macrophages specifically regulate the concentration of their own growth factor in the circulation. Proc Natl Acad Sci USA,1987,84:6179-6183.
51 Cecchini MG, Dominguez MG, Mocci S, et al. Role of colony stimulating factor-1 in the establishment and regulation of tissue macrophages during postnatal development of the mouse. Development,1994,120:1357-1372.
52 Dai XM, Zong XH, Sylvestre V, et al. Incomplete restoration of colony-stimulating factor 1 (CSF-1) function in CSF-1-deficient Csflop/Csflop mice by transgenic expression of cell surface CSF-1. Blood,2004,103:1114-1123.
53 Stanley ER. Colony-stimulating factor (CSF) radioimmunoassay:detection of a CSF subclass stimulating macrophage production. Proc Natl Acad Sci USA,1979,76: 2969-2973.
54 Nandi S, Akhter MP, Seifert MF, et al. Developmental and functional significance of the CSF-1 proteoglycan chondroitin sulfate chain. Blood,2006,107:786-795.
55 Jang MH, Herber DM, Jiang X, et al. Kelley distinct in vivo roles of colony-stimulating factor-1 isoforms in renal inflammation. J Immunol,2006,177: 4055-4063.
1 Angela Gallpo and Silvia Galardi. A-to-I RNA editing and cancer. RNA Biology, 2008,5(3):135-139.
2 Weier HU, George CX, Grenlich KM, et al. The interferon-inducible, double-stranded RNA-specific adenosine deaminase gene (DSRAD) maps to human chromosome 1q21.1-21.2. Genonucs,1995,30(2):372-375.
3 Kim U, Wang Y, Sanford T. et al. Molecular cloning of cDNA for double-stranded RNA adenosine deaminase, a candidate enzyme for nuclear RNA editing. Proc Natl Acad Sci USA,1994,91(24):11457-11461.
4 O'Connell MA, Krause S, Higuchi M. et al. Cloning of cDNAs encoding mammalian double-stranded RNA-specific adenosine deaminase. Mol Cell Biol,1995,15(3): 1389-1397.
5 Liu Y, George CX, Patterson JB, et al. Functionally distinct double-stranded RNA-binding domains associated with alternative splice site variants of the interferon-inducible double-stranded RNA-specific adenosine deaminase. J Biol Chem,1997,272(7):4419-4428.
6 Patterson JB, Samuel CE. Expression and regulation by interferon of a double-stranded-RNA-specific adenosine deaminase from human cells:evidence for two forms of the deaminase. Mol Cell Biol,1995,15(10):5376-5388.
7 George CX, Samuel CE. Human RNA-specie adenosine deaminase ADAR1 transcripts possess alternative exon 1 structures that initiate from different promoters, one constitutively active and the other interferon inducible. Proc Natl Acad Sci USA,1999,96(8):4621-4626.
8 Kawakubo K. Samuel CE. Human RNA-specific adenosine deaminase (ADAR1) gene specifies transcripts that initiate from a constitutively active alternative promoter. Gene,2000,258(1-2):165-172.
9 Yang JH, Nie Y, Zhao Q, et al. Intracellular localization of differentially regulated RNA-specific adenosine deaminase isoforms in inflammation. J Biol Chem,2003, 278(46):45833-45842.
10 Macbeth MR, Schubert HL, Vandemark AP, Lingam AT, Hill CP, Bass BL. Inositol hexakisphosphate is bound in the ADAR2 core and required for RNA editing. Science,2005,309:1534-1539.
11 Wagner RW, Yoo C, Wrabetz L, Kamholz J, Buchhalter J, Hassan NF, Khalili K, Kim SU, Perussia B, McMorris FA and Nishikura K. Double-stranded RNA unwinding and modifying activity is detected ubiquitously in primary tissues and cell lines. Mol Cell Biol,1990,10:5586-5590.
12 Liu Y, George CX, Patterson JB and Samuel CE. Functionally distinct double-stranded RNA-binding domains associated with alternative splice site variants of the interferon-inducible double-stranded RNA-specific adenosine deaminase. J Biol Chem.1997,272:4419-4428.
13 Gerber A, O'Connell MA and Keller W. Two forms of human double-stranded RNA-specific editase 1 (hRED1) generated by the insertion of an Alu cassette. RNA,1997,3:453-463.
14 Higuchi M. Maas S, Single FN, et al. Point mutation in an AMPA receptor gene rescues lethality in mice deficient in the RNA-editing enzyme ADAR2. Nature, 2000,406(6791):78-81.
15 Chen CX, Cho DS, Wang Q, et al. A third member of the RNA-specific adenosine deaminase gene family, ADAR3, contains both single-and double-stranded RNA binding domains. RNA,2000,6:755-767.
16 Melcher T, Maas S, Herb A, Sprengel R, Higuchi M and Seeburg PH. RED2, a brain-specific member of the RNA-specific adenosine deaminase family. J Biol Chem,1996,271:31795-31798.
17 Chilibeck KA, WuT, Liang C, Schellenberg MJ, Gesner EM, Lynch JM and MacMillan AM. FRET analysis of in vivo dimerization by RNA-editing enzymes. J Bio Chem,2006,281:16530-16535.
18 Gallo A, Keegan LP, Ring GM and O'Connell MA. An ADAR that edits transcripts encoding ion channel subunits functions as a dimer. EMBO J,2003, 22:3421-3430.
19 Poulsen H, Jorgensen R, Heding A, Nielsen FC, Bonven B and Egebjerg J. Dimerization of ADAR2 is mediated by the double-stranded RNA binding domain. RNA,2006,12:1350-1360.
20 Cho DS, Yang W, Lee JT, Shiekhattar R, Murray JM and Nishikura K. Requirement of dimerization for RNA editing activity of adenosine deaminases acting on RNA. J Biol Chem,2003,278:17093-17102.
21 Cenci C, Barzotti R, Galeano F, Corbelli S, Rota R, Massimi L, Di Rocco C, O'Connell MA, Gallo A. Down regulation of RNA editing in pediatric astrocytomas:ADAR2 editing activity inhibits cell migration and proliferation. J Biol Chem,2008,283:7251-7260.
22 Gerber AP, Keller W. An adenosine deaminase that generates inosine at the wobble position of tRNAs. Science,1999,286:1146-1149.
23 Gerber A, Grosjean H, Melcher T, Keller W. Tadlp, a yeast tRNA-specific adenosine deaminase, is related to the mammalian pre-mRNA editing enzymes ADAR1 and ADAR2. EMBOJ,1998,17:4780-4789.
24 Maas S, Gerber AP, Rich A. Identification and characterization of a human tRNA-specific adenosine deaminase related to the ADAR family of pre-mRNA editing enzymes. Proc Natl Acad Sci USA,1999,96:8895-8900.
25 Keegan LP, Gerber AP, Brindle J, Leemans R, Gallo A, et al. The properties of a tRNA-specific adenosine deaminase from Drosophila melanogaster support an evolutionary link between pre-mRNA editing and tRNA modification. Mol Cell Biol,2000,20:825-833.
26 Morse DP, Aruscavage P J, Bass BL, et al. RNA hairpins in noncoding regions of human brain and Caenorhabditis elegans mRNA are edited by adenosine deam-inases that act on RNA. Proc Natl Acad Sci USA,2002,99(12):7906-7911.
27 Mendell JT. miRiad roles for the miR-17-92 cluster in development and disease. Cell 2008;133:217-22.
28 Luciano DJ, Mirsky H, Vendetti NJ, Maas S. RNA editing of a miRNA precursor. RNA,2004,10:1174-1177.
29 Blow MJ, Grocock RJ, van Dongen S, Enright AJ, Dicks E, Futreal PA, Wooster R, Stratton MR. RNA editing of human microRNAs. Genome Biol,2006,7: 27.
30 Pfeffer S, Sewer A, Lagos-Quintana M, Sheridan R, Sander C, Grasser FA, van Dyk LF, Ho CK,Shuman S, Chien M, Russo JJ, Ju J, Randall G, Lindenbach BD, Rice CM, Simon V, Ho DD,Zavolan M, Tuschl T. Identification of microRNAs of the herpesvirus family. Nat Methods,2005,2:269-276.
31 Kawahara Y, Zinshteyn B, Sethupathy P, lizasa H, Hatzigeorgiou AG, Nishikura K. Redirection of silencing targets by adenosine-to-inosine editing of miRNAs. Science,2007,315:1137-1140.
32 Kawahara Y, Zinshteyn B, Chendrimada TP, Shiekhattar R, Nishikura K. RNA editing of the microRNA-151 precursor blocks cleavage by the Dicer-TRBP complex. EMBO Rep,2007,8:763-769.
33 Seeburg PH. A-to-I editing:new and old sites, functions and speculations. Neuron, 2002,35(1):17-20.
34 Maas S, Rich A, Nishikura K, et al. A-to-I RNA editing:recent news and residual mysteries. J Biol Chem,2003,278(3):11391-1394.
35 Poison AG, Bass BL, Casey JL. RNA editing of hepatitis delta virus antigenome by dsRNA-adenosine deaminase. Nature,1996,380(6573):454-456.
36 Scadden AD. Smith CW. A ribonuclease specific for inosine-containing RNA:a potential role in antiviral defence? EMBOJ,1997,16(8):2140-2149.
37 Rabinovici R, Kabir K, Chen M. et al. ADAR1 is involved in the development of microvascular lung injury. Circ Res,2001,88(10):1066-1071.
38 Yang JH, Luo X, Nie Y, et al. Widespread inosine-containing mRNA in lymphocytes regulated by ADAR1 in response to inflammation. Immunology, 2003,109(1):15-23.
39 Herbert A. Wagner S, Nickerson JA. Induction of protein translation by ADAR1 within living cell nuclei is not dependent on RNA editing. Mol Cell,2002,10(5): 1235-1246.
40 Lund E, Dahlberg JE. Proofreading and aminoacylation of tRNAs before export from the nucleus. Science,1998,282(5396):2082-2085.
41 Pederson T, Politz JC. The nucleolus and the four ribonucleoproteins of translation. J Cell Biol,2000,148(6):1091-1096.
42 lborra FJ, Jackson DA, Cook PR. Coupled transcription and translation within nuclei of mammalian cells. Science,2001,293:1139-1142.
43 Maas S, Patt S, Schrey M, Rich A. Underediting of glutamate receptor GluR-B mRNA in malignant gliomas. Proc Natl Acad Sci USA,2001,98:14687-14692.
44 Rickert CH, Paulus W. Epidemiology of central nervous system tumors in childhood and adolescence based on the new WHO classification. Childs Nerv Syst,2001,17:503-511.
45 Cohen KJ, Broniscer A, Glod J. Pediatric glial tumors. Curr Treat Options Oncol, 2001,2:529-536.
46 Wang Q, Khilan J, Gadue P, et al. Requirement of the RNA editing deaminase ADARl gene for embryonic erythropoiesis. Science,2000,290(5497):17651776.
47 Wang Q, Miyakoda M, Yang W, et al. Stress-induced apoptosis associated with null mutation of ADAR1 RNA editing deaminase gene. J Biol Chem,2004,279(6): 4952-4961.
48 Hartner JC, Schimittwolf C, Kispert A, et al. Liver disintegration in the mouse embryo caused by deficiency in the RNA editing enzyme ADAR1. J Biol Chem, 2004,279(6):4894-4902.
49 Hartner JC, Walkley CR, Lu J, Orkin SH. ADARl is essential for the maintenance of hematopoiesis and suppression of interferon signaling. Nat Immunol,2009,10: 109-115.
50 Richard XuFeng, Matthew J, Boyer, Hongmei Shen, Yanxin Li, Hui Yu, Yindai Gao, Qiong Yang, Qingde Wang, and Tao Cheng. ADAR1 is required for hematopoietic progenitor cell survival via RNA editing. PNAS,2009,106 (42):17763-17768.
51 Beghini A, Ripamonti CB, Peterlongo P, Roversi G, Cairoli R, Morra E, et al. RNA hyperediting and alternative splicing of hematopoietic cell phosphatase (PTPN6) gene in acute myeloid leukemia. Hum Mol Genet,2000,9:2297-2304.
52 Paz N, Levanon EY, Amariglio N, Heimberger AB, Ram Z, Constantini S, et al. Altered adenosine-to-inosine RNA editing in human cancer. Genome Res, 2007,17:1586-1595.
53 Wang Q, Miyakoda M, Yang W, Khillan J, Stachura DL, Weiss MJ, Nishikura K. Stress-induced apoptosis associated with null mutation of ADAR1 RNA editing deaminase gene. J Biol Chem,2004,279:4952-4961.
54 Wang Y, Samuel CE. Adenosine deaminase ADARl increases gene expression at the translational level by decreasing protein kinase PKR-dependent eIF-2a phosphorylation. J Mol Biol,2009,393:777-787.
55 Zhang XJ, Gao M, Li M, et al. Identification of a locus for dyschromatosis symmetrica hereditaria at chromosome 1q11-1q21. J Invest Dermatol,2003, 120(5):776-780.
56 Miyamura Y, Suzuki T, Kono M, et al. Mutations of the RNA-specific adenosine deaminase gene (DSRAD) are involved in dyschromatosis symmetrica hereditaria. Am J Ham Genet,2003,73(3):693-699.
57 Liu Q, Liu WL, Jiang L, et al. Novel Mutations of the RNA-Specific Adenosine Deaminase Gene (DSRAD)in Chinese Families with Dyschromatosis Symmetrica Hereditaria. J Invest Dermatol,2004,122(4):896-899.
58 Furen Zhang, Hong Liu, Deke Jiang, Hongqing Tian, Changyuan Wang, Long Yu. Six novel mutations of the ADAR1 gene in Chinese patients with dyschromatosis symmetrica hereditaria Journal of Dermatological Science,2008, 50:109-114.
59 Ming Li, Lijia Yang, Chengrang Li, Cheng Jin, Meiling Lai, Guolong Zhang, Yan Hu, Jin ji, Zhirong Yao. Mutational spectrum of the ADAR1 gene in dyschromatosis symmetrica hereditaria. Arch Dermatol Res,2010,302:469-476.