桥粒相关蛋白Pinin的生物学功能及其在肿瘤发生中的作用
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摘要
桥粒不但参与上皮和心肌细胞的连接,增强细胞承受机械应力时的黏附作用,还能调控细胞行为和组织形态发生改变时的信号传导通路过程.桥粒相关蛋白Pinin(PNN)自发现以来,其位置和功能就备受争议.现有结果表明,PNN包含与细胞膜上桥粒共定位的桥粒型PNN和位于细胞核中的核型PNN两种,前者参与上皮细胞的黏附,后者与m RNA的选择性剪接功能有关.新近研究发现,PNN与肿瘤发生密切相关,然而其作用及其分子机制却不相同.本文对PNN的结构、功能及其与肿瘤发生的关系作一综述.
Desmosome not only participates in the connections of epithelial cell and cardiomyocyte to enhance the cell adhesion when subjected to mechanical stress, it also regulates signal pathways of cell behavior. Since the discovery of Pinin(PNN), a desmosome-associated protein, its position and function are controversial. Current results indicate that PNN has two types: a desmosome-like PNN co-localized with desmosomes on the cell membrane, and a karyotype PNN located in the nucleus. The former participates in epithelial cell adhesion, the latter is related to the alternative splicing function of genes. Recent studies have found that PNN is closely related to tumorigenesis via different molecular mechanism. This article reviews the biological function of PNN and its relationship with tumorigenesis.
Desmosome not only participates in the connections of epithelial cell and cardiomyocyte to enhance the cell adhesion when subjected to mechanical stress, it also regulates signal pathways of cell behavior. Since the discovery of Pinin(PNN), a desmosome-associated protein, its position and function are controversial. Current results indicate that PNN has two types: a desmosome-like PNN co-localized with desmosomes on the cell membrane, and a karyotype PNN located in the nucleus. The former participates in epithelial cell adhesion, the latter is related to the alternative splicing function of genes. Recent studies have found that PNN is closely related to tumorigenesis via different molecular mechanism. This article reviews the biological function of PNN and its relationship with tumorigenesis.
引文
[1]Najor N A.Desmosomes in human disease.Annual Review of Pathology,2018,13(1):51-70
[2]Chidgey M,Dawson C.Desmosomes:a role in cancer？British Journal of Cancer,2007,96(12):1783-1787
[3]Rietscher K,Keil R,Jordan A,et al.14-3-3 proteins regulate desmosomal adhesion via plakophilins.Journal of Cell Science,2018,131(10):1-13
[4]Garrod D,Chidgey M,North A.Desmosomes:differentiation,development,dynamics and disease.Current Opinion in Cell Biology,1996,8(5):670-678
[5]Cirillo N.150th anniversary series:desmosomes in physiology and disease.Cell Communication&Adhesion,2014,21(2):85-88
[6]Polivka L,Hadjrabia S,Bal E,et al.Epithelial barrier dysfunction in Desmoglein-1 deficiency.Journal of Allergy&Clinical Immunology,2018,142(2):702-706
[7]Hammers C M,Stanley J R.Desmoglein-1,differentiation,and disease.Journal of Clinical Investigation,2013,123(4):1419-1422
[8]Alaee M,Nool K,Pasdar M.Plakoglobin restores tumor suppressor activity of p53R175H mutant by sequestering the oncogenic potential ofβ-catenin.Cancer Science,2018,109(6):1876-1888
[9]Rotemberg V,Garzon M,Lauren C,et al.A novel mutation in junctional plakoglobin causing lethal congenital epidermolysis bullosa.Journal of Pediatrics,2017,191:266-269
[10]Giuliodori A,Beffagna G,Marchetto G,et al.Loss of cardiac Wnt/?2-catenin signalling in Desmoplakin-deficient AC8 zebrafish models is rescuable by genetic and pharmacological intervention.Cardiovascular Research,2018,114(8):1082-1097
[11]Abreuvelez A M,Valenciayepes C A,Upeguizapata Y A,et al.Patients with a new variant of endemic pemphigus foliaceus have autoantibodies against arrector pili muscle,colocalizing with MYZAP,p0071,desmoplakins 1 and 2 and ARVCF.Clinical&Experimental Dermatology,2017,42(8):874-880
[12]Ouyang P,Sugrue S P.Identification of an epithelial protein related to the desmosome and intermediate filament network.Journal of Cell Biology,1992,118(6):1477-1488
[13]Ouyang P,Sugrue S P.Characterization of pinin,a novel protein associated with the desmosome-intermediate filament complex.Journal of Cell Biology,1996,135(4):1027-1042
[14]Brandner J M,Reidenbach S,Kuhn C,et al.Identification and characterization of a novel kind of nuclear protein occurring free in the nucleoplasm and in ribonucleoprotein structures of the"speckle"type.European Journal of Cell Biology,1998,75(4):295-308
[15]Degen W G,Agterbos M A,Muyrers J P,et al.memA/DRS,a putative mediator of multiprotein complexes,is overexpressed in the metastasizing human melanoma cell lines BLM and MV3.Biochimica Et BiophysicaActa,1999,1444(3):384-394
[16]Shi Y,Ouyang P,Sugrue S P.Characterization of the gene encoding pinin/DRS/memA and evidence for its potential tumor suppressor function.Oncogene,2000,19(2):289-297
[17]Ouyang P.Antibodies differentiate desmosome-form and nucleusform pinin:evidence that pinin is a moonlighting protein with dual location at the desmosome and within the nucleus.Biochemical&Biophysical Research Communications,1999,263(1):192-200
[18]Hsu S Y,Chen Y J,Ouyang P.Pnn and SR family proteins are differentially expressed in mouse central nervous system.Histochemistry&Cell Biology,2011,135(4):361-373
[19]Hsu S Y,Cheng Y C,Shih H Y,et al.Dissection of the role of Pinin in the development of zebrafish posterior pharyngeal cartilages.Histochemistry&Cell Biology,2012,138(1):127-140
[20]Simmons M N.Change in gene expression subsequent to induction of Pnn/DRS/memA:increase in p21cip1/waf1.Oncogene,2001,20(30):4007-4018
[21]Shi J,Sugrue S P.Dissection of protein linkage between keratins and pinin,a protein with dual location at desmosome-intermediate filament complex and in the nucleus.Journal of Biological Chemistry,2000,275(20):14910-14915
[22]Shi Y,Tabesh M,Sugrue S P.Role of cell adhesion-associated protein,pinin(DRS/memA),in corneal epithelial migration.Investigative Ophthalmology&Visual Science,2000,41(6):1337-1345
[23]Joo J H,Alpatov R,Munguba G C,et al.Reduction of Pnn by RNAi induces loss of cell-cell adhesion between human corneal epithelial cells.Molecular Vision,2005,11(15):133-142
[24]Zimowska G,Shi J,Munguba G,et al.Pinin/DRS/memA interacts with SRp75,SRm300 and SRrp130 in corneal epithelial cells.Investigative Ophthalmology&Visual Science,2003,44(11):4715-4723
[25]Jeong-Hoon J,Correia G P,Jian-Liang L,et al.Transcriptomic analysis of PNN-and ESRP1-regulated alternative pre-mRNAsplicing in human corneal epithelial cells.Investigative Ophthalmology&Visual Science,2013,54(1):697-707
[26]Murachelli A G,Ebert J,Basquin C,et al.The structure of the ASAP core complex reveals the existence of a Pinin-containing PSAP complex.Nature Structural&Molecular biology,2012,19(4):378-386
[27]Joo J H,Ryu D,Peng Q,et al.Role of Pnn in alternative splicing of a specific subset of lncRNAs of the corneal epithelium.Molecular Vision,2014,20(32):1629-1642
[28]Akin D,Newman J R,Mcintyre L M,et al.RNA-seq analysis of impact of PNN on gene expression and alternative splicing in corneal epithelial cells.Molecular Vision,2016,22:40-60
[29]Zhang Y,Kwok J S,Choi P W,et al.Pinin interacts with C-terminal binding proteins for RNA alternative splicing and epithelial cell identity of human ovarian cancer cells.Oncotarget,2016,7(10):11397-11411
[30]Yang X,Sun D,Dong C,et al.Pinin associates with prognosis of hepatocellular carcinoma through promoting cell proliferation and suppressing glucose deprivation-induced apoptosis.Oncotarget,2016,7(26):39694-39704
[31]Wei Z,Ma W,Qi X,et al.Pinin facilitated proliferation and metastasis of colorectal cancer through activating EGFR/ERKsignaling pathway.Oncotarget,2016,7(20):29429-29439
[32]Leu S,Ouyang P.Spatial and temporal expression profile of pinin during mouse development.Gene Expression Patterns,2006,6(6):620-631
[33]Leu S,Lin Y M,Wu C H,et al.Loss of Pnn expression results in mouse early embryonic lethality and cellular apoptosis through SRSF1-mediated alternative expression of Bcl-xS and ICAD.Journal of Cell Science,2012,125(pt13):3164-3172
[2]Chidgey M,Dawson C.Desmosomes:a role in cancer？British Journal of Cancer,2007,96(12):1783-1787
[3]Rietscher K,Keil R,Jordan A,et al.14-3-3 proteins regulate desmosomal adhesion via plakophilins.Journal of Cell Science,2018,131(10):1-13
[4]Garrod D,Chidgey M,North A.Desmosomes:differentiation,development,dynamics and disease.Current Opinion in Cell Biology,1996,8(5):670-678
[5]Cirillo N.150th anniversary series:desmosomes in physiology and disease.Cell Communication&Adhesion,2014,21(2):85-88
[6]Polivka L,Hadjrabia S,Bal E,et al.Epithelial barrier dysfunction in Desmoglein-1 deficiency.Journal of Allergy&Clinical Immunology,2018,142(2):702-706
[7]Hammers C M,Stanley J R.Desmoglein-1,differentiation,and disease.Journal of Clinical Investigation,2013,123(4):1419-1422
[8]Alaee M,Nool K,Pasdar M.Plakoglobin restores tumor suppressor activity of p53R175H mutant by sequestering the oncogenic potential ofβ-catenin.Cancer Science,2018,109(6):1876-1888
[9]Rotemberg V,Garzon M,Lauren C,et al.A novel mutation in junctional plakoglobin causing lethal congenital epidermolysis bullosa.Journal of Pediatrics,2017,191:266-269
[10]Giuliodori A,Beffagna G,Marchetto G,et al.Loss of cardiac Wnt/?2-catenin signalling in Desmoplakin-deficient AC8 zebrafish models is rescuable by genetic and pharmacological intervention.Cardiovascular Research,2018,114(8):1082-1097
[11]Abreuvelez A M,Valenciayepes C A,Upeguizapata Y A,et al.Patients with a new variant of endemic pemphigus foliaceus have autoantibodies against arrector pili muscle,colocalizing with MYZAP,p0071,desmoplakins 1 and 2 and ARVCF.Clinical&Experimental Dermatology,2017,42(8):874-880
[12]Ouyang P,Sugrue S P.Identification of an epithelial protein related to the desmosome and intermediate filament network.Journal of Cell Biology,1992,118(6):1477-1488
[13]Ouyang P,Sugrue S P.Characterization of pinin,a novel protein associated with the desmosome-intermediate filament complex.Journal of Cell Biology,1996,135(4):1027-1042
[14]Brandner J M,Reidenbach S,Kuhn C,et al.Identification and characterization of a novel kind of nuclear protein occurring free in the nucleoplasm and in ribonucleoprotein structures of the"speckle"type.European Journal of Cell Biology,1998,75(4):295-308
[15]Degen W G,Agterbos M A,Muyrers J P,et al.memA/DRS,a putative mediator of multiprotein complexes,is overexpressed in the metastasizing human melanoma cell lines BLM and MV3.Biochimica Et BiophysicaActa,1999,1444(3):384-394
[16]Shi Y,Ouyang P,Sugrue S P.Characterization of the gene encoding pinin/DRS/memA and evidence for its potential tumor suppressor function.Oncogene,2000,19(2):289-297
[17]Ouyang P.Antibodies differentiate desmosome-form and nucleusform pinin:evidence that pinin is a moonlighting protein with dual location at the desmosome and within the nucleus.Biochemical&Biophysical Research Communications,1999,263(1):192-200
[18]Hsu S Y,Chen Y J,Ouyang P.Pnn and SR family proteins are differentially expressed in mouse central nervous system.Histochemistry&Cell Biology,2011,135(4):361-373
[19]Hsu S Y,Cheng Y C,Shih H Y,et al.Dissection of the role of Pinin in the development of zebrafish posterior pharyngeal cartilages.Histochemistry&Cell Biology,2012,138(1):127-140
[20]Simmons M N.Change in gene expression subsequent to induction of Pnn/DRS/memA:increase in p21cip1/waf1.Oncogene,2001,20(30):4007-4018
[21]Shi J,Sugrue S P.Dissection of protein linkage between keratins and pinin,a protein with dual location at desmosome-intermediate filament complex and in the nucleus.Journal of Biological Chemistry,2000,275(20):14910-14915
[22]Shi Y,Tabesh M,Sugrue S P.Role of cell adhesion-associated protein,pinin(DRS/memA),in corneal epithelial migration.Investigative Ophthalmology&Visual Science,2000,41(6):1337-1345
[23]Joo J H,Alpatov R,Munguba G C,et al.Reduction of Pnn by RNAi induces loss of cell-cell adhesion between human corneal epithelial cells.Molecular Vision,2005,11(15):133-142
[24]Zimowska G,Shi J,Munguba G,et al.Pinin/DRS/memA interacts with SRp75,SRm300 and SRrp130 in corneal epithelial cells.Investigative Ophthalmology&Visual Science,2003,44(11):4715-4723
[25]Jeong-Hoon J,Correia G P,Jian-Liang L,et al.Transcriptomic analysis of PNN-and ESRP1-regulated alternative pre-mRNAsplicing in human corneal epithelial cells.Investigative Ophthalmology&Visual Science,2013,54(1):697-707
[26]Murachelli A G,Ebert J,Basquin C,et al.The structure of the ASAP core complex reveals the existence of a Pinin-containing PSAP complex.Nature Structural&Molecular biology,2012,19(4):378-386
[27]Joo J H,Ryu D,Peng Q,et al.Role of Pnn in alternative splicing of a specific subset of lncRNAs of the corneal epithelium.Molecular Vision,2014,20(32):1629-1642
[28]Akin D,Newman J R,Mcintyre L M,et al.RNA-seq analysis of impact of PNN on gene expression and alternative splicing in corneal epithelial cells.Molecular Vision,2016,22:40-60
[29]Zhang Y,Kwok J S,Choi P W,et al.Pinin interacts with C-terminal binding proteins for RNA alternative splicing and epithelial cell identity of human ovarian cancer cells.Oncotarget,2016,7(10):11397-11411
[30]Yang X,Sun D,Dong C,et al.Pinin associates with prognosis of hepatocellular carcinoma through promoting cell proliferation and suppressing glucose deprivation-induced apoptosis.Oncotarget,2016,7(26):39694-39704
[31]Wei Z,Ma W,Qi X,et al.Pinin facilitated proliferation and metastasis of colorectal cancer through activating EGFR/ERKsignaling pathway.Oncotarget,2016,7(20):29429-29439
[32]Leu S,Ouyang P.Spatial and temporal expression profile of pinin during mouse development.Gene Expression Patterns,2006,6(6):620-631
[33]Leu S,Lin Y M,Wu C H,et al.Loss of Pnn expression results in mouse early embryonic lethality and cellular apoptosis through SRSF1-mediated alternative expression of Bcl-xS and ICAD.Journal of Cell Science,2012,125(pt13):3164-3172