肝再生磷酸酶-2的分子结构与功能研究进展
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摘要
肝再生磷酸酶-2 (PRL-2)在机体正常的细胞、组织和器官,以及大部分的肿瘤中普遍高表达,以其致癌原性被广泛认知,但分子机制尚不明确。近几年的研究发现了PRL-2的新型结合伴侣——细胞周期蛋白M (cyclin-M, CNNM)家族,为进一步解析PRL-2的生理生物功能提供新的方向。现总结PRL-2分子在实体瘤、血液肿瘤中的作用,探讨其结构与功能的关系,并对PRL-2及其结合伴侣的生理功能进行全面综述。
Phosphatase of regenerative liver-2(PRL-2), which is well known for its carcinogenicity, is highly expressed in normal cells, tissues and organs, as well as in most tumors, but the molecular mechanism is still unclear. Recent studies have found a new binding partner of PRL-2: cyclin-M(CNNM) family, which provides a new direction for further research about the physiological and biological functions of PRL-2. This review summarizes the current understanding of the role of PRL-2 in solid tumors and hematological tumors, explores the relationship between its structure and function, and comprehensively reviews the physiological functions of PRL-2 and its binding partners.
Phosphatase of regenerative liver-2(PRL-2), which is well known for its carcinogenicity, is highly expressed in normal cells, tissues and organs, as well as in most tumors, but the molecular mechanism is still unclear. Recent studies have found a new binding partner of PRL-2: cyclin-M(CNNM) family, which provides a new direction for further research about the physiological and biological functions of PRL-2. This review summarizes the current understanding of the role of PRL-2 in solid tumors and hematological tumors, explores the relationship between its structure and function, and comprehensively reviews the physiological functions of PRL-2 and its binding partners.
引文
[1]Diamond RH,Cressman DE,Laz TM,et al.PRL-1,a unique nuclear protein tyrosine phosphatase,affects cell growth.Mol Cell Biol,1994,14:3752-62
[2]Werner SR,Lee PA,DeCamp MW,et al.Enhanced cell cycle progression and down regulation of p21(Cip1/Waf1)by PRL tyrosine phosphatases.Cancer Lett,2003,202:201-11
[3]Bessette DC,Qiu D,Pallen CJ.PRL PTPs:mediators and markers of cancer progression.Cancer Metastasis Rev,2008,27:231-52
[4]Wang J,Kirby CE,Herbst R.The tyrosine phosphatase PRL-1 localizes to the endoplasmic reticulum and the mitotic spindle and is required for normal mitosis.J Biol Chem,2002,277:46659-68
[5]Sun JP,Wang WQ,Yang H,et al.Structure and biochemical properties of PRL-1,a phosphatase implicated in cell growth,differentiation,and tumor invasion.Biochemistry,2005,44:12009-21
[6]Hardy S,Wong NN,Muller WJ,et al.Overexpression of the protein tyrosine phosphatase PRL-2 correlates with breast tumor formation and progression.Cancer Res,2010,70:8959-67
[7]Si X,Zeng Q,Ng CH,et al.Interaction of farnesylated PRL-2,a protein-tyrosine phosphatase,with theβ-subunit of geranylgeranyltransferase II.J Biol Chem,2001,276:32875-82
[8]Tonks NK.Redox redux:revisiting PTPs and the control of cell signaling.Cell,2005,121:667-70
[9]Orsatti L,Innocenti F,Lo Surdo P,et al.Mass spectrometry study of PRL-3 phosphatase inactivation by disulfide bond formation and cysteine into glycine conversion.Rapid Commun Mass Spectrom,2009,23:2733-40
[10]Hardy S,Kostantin E,Hatzihristidis T,et al.Physiological and oncogenic roles of the PRL phosphatases.FEBS J,2018,285:3886-908
[11]Ishii T,Funato Y,Miki H.Thioredoxin-related protein 32(TRP32)specifically reduces oxidized phosphatase of regenerating liver(PRL).J Biol Chem,2013,288:7263-70
[12]Yu L,Kelly U,Ebright JN,et al.Oxidative stress-induced expression and modulation of phosphatase of regenerating liver-1(PRL-1)in mammalian retina.Biochim Biophys Acta,2007,1773:1473-82
[13]Ostman A,Frijhoff J,Sandin A,et al.Regulation of protein tyrosine phosphatases by reversible oxidation.JBiochem,2011,150:345-56
[14]Sun JP,Luo Y,Yu X,et al.Phosphatase activity,trimerization,and the C-terminal polybasic region are all required for PRL1-mediated cell growth and migration.JBiol Chem,2007,282:29043-51
[15]Cates CA,Michael RL,Stayrook KR,et al.Prenylation of oncogenic human PTP(CAAX)protein tyrosine phosphatases.Cancer Lett,1996,110:49-55
[16]Pascaru M,Tanase C,Vacaru AM,et al.Analysis of molecular determinants of PRL-3.J Cell Mol Med,2009,13:3141-50
[17]Skinner AL,Vartia AA,Williams TD,et al.Enzyme activity of phosphatase of regenerating liver is controlled by the redox environment and its C-terminal residues.Biochemistry,2009,48:4262-72
[18]Wang Y,Lazo JS.Metastasis-associated phosphatase PRL-2 regulates tumor cell migration and invasion.Oncogene,2012,31:818-27
[19]Zeng Q,Si X,Horstmann H,et al.Prenylation-dependent association of protein-tyrosine phosphatases PRL-1,-2,and-3 with the plasma membrane and the early endosome.J Biol Chem,2000,275:21444-52
[20]Kozlov G,Cheng J,Ziomek E,et al.Structural insights into molecular function of the metastasis-associated phosphatase PRL-3.J Biol Chem,2004,279:11882-9
[21]Dong Y,Zhang L,Zhang S,et al.Phosphatase of regenerating liver 2(PRL2)is essential for placental development by down-regulating PTEN(phosphatase and tensin homologue deleted on chromosome 10)and activating Akt protein.J Biol Chem,2012,287:32172-9
[22]Bai Y,Zhou HM,Zhang L,et al.Role of phosphatase of regenerating liver 1(PRL1)in spermatogenesis.Sci Rep,2016,6:34211
[23]Kobayashi M,Bai Y,Dong Y,et al.PRL2/PTP4A2phosphatase is important for hematopoietic stem cell selfrenewal.Stem Cells,2014,32:1956-67
[24]Kobayashi M,Nabinger SC,Bai Y,et al.Protein tyrosine phosphatase PRL2 mediates Notch and Kit signals in early T cell progenitors.Stem Cells,2017,35:1053-64
[25]Dong Y,Zhang L,Bai Y,et al.Phosphatase of regenerating liver 2(PRL2)deficiency impairs Kit signaling and spermatogenesis.J Biol Chem,2014,289:3799-810
[26]Yin C,Wu C,Du X,et al.PRL2 controls phagocyte bactericidal activity by sensing and regulating ROS.Front Immunol,2018,9:2609
[27]Fiordalisi JJ,Keller PJ,Cox AD.PRL tyrosine phosphatases regulate Rho family GTPases to promote invasion and motility.Cancer Res,2006,66:3153-61
[28]Wu X,Zeng H,Zhang X,et al.Phosphatase of regenerating liver-3 promotes motility and metastasis of mouse melanoma cells.Am J Pathol,2004,164:2039-54
[29]Zeng Q,Dong JM,Guo K,et al.PRL-3 and PRL-1promote cell migration,invasion,and metastasis.Cancer Res,2003,63:2716-22
[30]Wang Q,Holmes DI,Powell SM,et al.Analysis of stromal-epithelial interactions in prostate cancer identifies PTPCAAX2 as a potential oncogene.Cancer Lett,2002,175:63-9
[31]Stephens B,Han H,Hostetter G,et al.Small interfering RNA-mediated knockdown of PRL phosphatases results in altered Akt phosphorylation and reduced clonogenicity of pancreatic cancer cells.Mol Cancer Ther,2008,7:202-10
[32]Kobayashi M,Chen S,Bai Y,et al.Phosphatase PRL2promotes AML1-ETO-induced acute myeloid leukemia.Leukemia,2017,31:1453-7
[33]Stephens BJ,Han H,Gokhale V,et al.PRL phosphatases as potential molecular targets in cancer.Mol Cancer Ther,2005,4:1653-61
[34]Andres SA,Wittliff JL,Cheng A.Protein tyrosine phosphatase 4A2 expression predicts overall and diseasefree survival of human breast cancer and is associated with estrogen and progestin receptor status.Horm Cancer,2013,4:208-21
[35]Zhao D,Libin G,Neves H,et al.The prognostic significance of protein tyrosine phosphatase 4A2 in breast cancer.Oncol Targets Ther,2015,8:1707-17
[36]Akiyama S,Dhavan D,Yi T.PRL-2 increases Epo and IL-3 responses in hematopoietic cells.Blood Cells Mol Dis,2010,44:209-14
[37]Gao Y.Over-expression of protein tyrosine phosphatase4A2 correlates with tumor progression and poor prognosis in nasopharyngeal carcinoma.Oncotarget,2017,8:77527-39
[38]Reich R,Hadar S,Davidson B.Expression and clinical role of protein of regenerating liver(PRL)phosphatases in ovarian carcinoma.Int J Mol Sci,2011,12:1133-45
[39]Hardy S,Uetani N,Wong N,et al.The protein tyrosine phosphatase PRL-2 interacts with the magnesium transporter CNNM3 to promote oncogenesis.Oncogene,2015,34:986-95
[40]Gulerez I,Funato Y,Wu H,et al.Phosphocysteine in the PRL-CNNM pathway mediates magnesium homeostasis.EMBO Rep,2016,17:1890-900
[41]Zhang H,Kozlov G,Li X,et al.PRL3 phosphatase active site is required for binding the putative magnesium transporter CNNM3.Sci Rep,2017,7:48
[42]Kostantin E,Hardy S,Valinsky WC,et al.Inhibition of PRL-2·CNNM3 protein complex formation decreases breast cancer proliferation and tumor growth.J Biol Chem,2016,291:10716-25
[43]Gungabeesoon J,Tremblay ML,Uetani N.Localizing PRL-2 expression and determining the effects of dietary Mg2+on expression levels.Histochem Cell Biol,2016,146:99-111
[44]Uetani N,Hardy S,Gravel SP,et al.PRL2 links magnesium flux and sex-dependent circadian metabolic rhythms.JCIInsight,2017,2:e91722
[45]Pathak MK,Dhawan D,Lindner DJ,et al.Pentamidine is an inhibitor of PRL phosphatases with anticancer activity.Mol Cancer Ther,2002,1:1255-64
[46]Collaborators GMC.Global,regional,and national agesex specific mortality for 264 causes of death,1980-2016:a systematic analysis for the Global Burden of Disease Study 2016.Lancet,2017,390:1151-210
[47]Alonso A,Sasin J,Bottini N,et al.Protein tyrosine phosphatases in the human genome.Cell,2004,117:699-711
[48]Lin MD,Lee HT,Wang SC,et al.Expression of phosphatase of regenerating liver family genes during embryogenesis:an evolutionary developmental analysis among Drosophila,amphioxus,and zebrafish.BMC Dev Biol,2013,13:18
[49]Leitherer S,Clos J,Liebler-Tenorio EM,et al.Characterization of the protein tyrosine phosphatase LmPRL-1 secreted by Leishmania major via the exosome pathway.Infect Immun,2017,85:e00084-17
[50]Fagerberg L,Hallstrom BM,Oksvold P,et al.Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics.Mol Cell Proteomics,2014,13:397-406
[2]Werner SR,Lee PA,DeCamp MW,et al.Enhanced cell cycle progression and down regulation of p21(Cip1/Waf1)by PRL tyrosine phosphatases.Cancer Lett,2003,202:201-11
[3]Bessette DC,Qiu D,Pallen CJ.PRL PTPs:mediators and markers of cancer progression.Cancer Metastasis Rev,2008,27:231-52
[4]Wang J,Kirby CE,Herbst R.The tyrosine phosphatase PRL-1 localizes to the endoplasmic reticulum and the mitotic spindle and is required for normal mitosis.J Biol Chem,2002,277:46659-68
[5]Sun JP,Wang WQ,Yang H,et al.Structure and biochemical properties of PRL-1,a phosphatase implicated in cell growth,differentiation,and tumor invasion.Biochemistry,2005,44:12009-21
[6]Hardy S,Wong NN,Muller WJ,et al.Overexpression of the protein tyrosine phosphatase PRL-2 correlates with breast tumor formation and progression.Cancer Res,2010,70:8959-67
[7]Si X,Zeng Q,Ng CH,et al.Interaction of farnesylated PRL-2,a protein-tyrosine phosphatase,with theβ-subunit of geranylgeranyltransferase II.J Biol Chem,2001,276:32875-82
[8]Tonks NK.Redox redux:revisiting PTPs and the control of cell signaling.Cell,2005,121:667-70
[9]Orsatti L,Innocenti F,Lo Surdo P,et al.Mass spectrometry study of PRL-3 phosphatase inactivation by disulfide bond formation and cysteine into glycine conversion.Rapid Commun Mass Spectrom,2009,23:2733-40
[10]Hardy S,Kostantin E,Hatzihristidis T,et al.Physiological and oncogenic roles of the PRL phosphatases.FEBS J,2018,285:3886-908
[11]Ishii T,Funato Y,Miki H.Thioredoxin-related protein 32(TRP32)specifically reduces oxidized phosphatase of regenerating liver(PRL).J Biol Chem,2013,288:7263-70
[12]Yu L,Kelly U,Ebright JN,et al.Oxidative stress-induced expression and modulation of phosphatase of regenerating liver-1(PRL-1)in mammalian retina.Biochim Biophys Acta,2007,1773:1473-82
[13]Ostman A,Frijhoff J,Sandin A,et al.Regulation of protein tyrosine phosphatases by reversible oxidation.JBiochem,2011,150:345-56
[14]Sun JP,Luo Y,Yu X,et al.Phosphatase activity,trimerization,and the C-terminal polybasic region are all required for PRL1-mediated cell growth and migration.JBiol Chem,2007,282:29043-51
[15]Cates CA,Michael RL,Stayrook KR,et al.Prenylation of oncogenic human PTP(CAAX)protein tyrosine phosphatases.Cancer Lett,1996,110:49-55
[16]Pascaru M,Tanase C,Vacaru AM,et al.Analysis of molecular determinants of PRL-3.J Cell Mol Med,2009,13:3141-50
[17]Skinner AL,Vartia AA,Williams TD,et al.Enzyme activity of phosphatase of regenerating liver is controlled by the redox environment and its C-terminal residues.Biochemistry,2009,48:4262-72
[18]Wang Y,Lazo JS.Metastasis-associated phosphatase PRL-2 regulates tumor cell migration and invasion.Oncogene,2012,31:818-27
[19]Zeng Q,Si X,Horstmann H,et al.Prenylation-dependent association of protein-tyrosine phosphatases PRL-1,-2,and-3 with the plasma membrane and the early endosome.J Biol Chem,2000,275:21444-52
[20]Kozlov G,Cheng J,Ziomek E,et al.Structural insights into molecular function of the metastasis-associated phosphatase PRL-3.J Biol Chem,2004,279:11882-9
[21]Dong Y,Zhang L,Zhang S,et al.Phosphatase of regenerating liver 2(PRL2)is essential for placental development by down-regulating PTEN(phosphatase and tensin homologue deleted on chromosome 10)and activating Akt protein.J Biol Chem,2012,287:32172-9
[22]Bai Y,Zhou HM,Zhang L,et al.Role of phosphatase of regenerating liver 1(PRL1)in spermatogenesis.Sci Rep,2016,6:34211
[23]Kobayashi M,Bai Y,Dong Y,et al.PRL2/PTP4A2phosphatase is important for hematopoietic stem cell selfrenewal.Stem Cells,2014,32:1956-67
[24]Kobayashi M,Nabinger SC,Bai Y,et al.Protein tyrosine phosphatase PRL2 mediates Notch and Kit signals in early T cell progenitors.Stem Cells,2017,35:1053-64
[25]Dong Y,Zhang L,Bai Y,et al.Phosphatase of regenerating liver 2(PRL2)deficiency impairs Kit signaling and spermatogenesis.J Biol Chem,2014,289:3799-810
[26]Yin C,Wu C,Du X,et al.PRL2 controls phagocyte bactericidal activity by sensing and regulating ROS.Front Immunol,2018,9:2609
[27]Fiordalisi JJ,Keller PJ,Cox AD.PRL tyrosine phosphatases regulate Rho family GTPases to promote invasion and motility.Cancer Res,2006,66:3153-61
[28]Wu X,Zeng H,Zhang X,et al.Phosphatase of regenerating liver-3 promotes motility and metastasis of mouse melanoma cells.Am J Pathol,2004,164:2039-54
[29]Zeng Q,Dong JM,Guo K,et al.PRL-3 and PRL-1promote cell migration,invasion,and metastasis.Cancer Res,2003,63:2716-22
[30]Wang Q,Holmes DI,Powell SM,et al.Analysis of stromal-epithelial interactions in prostate cancer identifies PTPCAAX2 as a potential oncogene.Cancer Lett,2002,175:63-9
[31]Stephens B,Han H,Hostetter G,et al.Small interfering RNA-mediated knockdown of PRL phosphatases results in altered Akt phosphorylation and reduced clonogenicity of pancreatic cancer cells.Mol Cancer Ther,2008,7:202-10
[32]Kobayashi M,Chen S,Bai Y,et al.Phosphatase PRL2promotes AML1-ETO-induced acute myeloid leukemia.Leukemia,2017,31:1453-7
[33]Stephens BJ,Han H,Gokhale V,et al.PRL phosphatases as potential molecular targets in cancer.Mol Cancer Ther,2005,4:1653-61
[34]Andres SA,Wittliff JL,Cheng A.Protein tyrosine phosphatase 4A2 expression predicts overall and diseasefree survival of human breast cancer and is associated with estrogen and progestin receptor status.Horm Cancer,2013,4:208-21
[35]Zhao D,Libin G,Neves H,et al.The prognostic significance of protein tyrosine phosphatase 4A2 in breast cancer.Oncol Targets Ther,2015,8:1707-17
[36]Akiyama S,Dhavan D,Yi T.PRL-2 increases Epo and IL-3 responses in hematopoietic cells.Blood Cells Mol Dis,2010,44:209-14
[37]Gao Y.Over-expression of protein tyrosine phosphatase4A2 correlates with tumor progression and poor prognosis in nasopharyngeal carcinoma.Oncotarget,2017,8:77527-39
[38]Reich R,Hadar S,Davidson B.Expression and clinical role of protein of regenerating liver(PRL)phosphatases in ovarian carcinoma.Int J Mol Sci,2011,12:1133-45
[39]Hardy S,Uetani N,Wong N,et al.The protein tyrosine phosphatase PRL-2 interacts with the magnesium transporter CNNM3 to promote oncogenesis.Oncogene,2015,34:986-95
[40]Gulerez I,Funato Y,Wu H,et al.Phosphocysteine in the PRL-CNNM pathway mediates magnesium homeostasis.EMBO Rep,2016,17:1890-900
[41]Zhang H,Kozlov G,Li X,et al.PRL3 phosphatase active site is required for binding the putative magnesium transporter CNNM3.Sci Rep,2017,7:48
[42]Kostantin E,Hardy S,Valinsky WC,et al.Inhibition of PRL-2·CNNM3 protein complex formation decreases breast cancer proliferation and tumor growth.J Biol Chem,2016,291:10716-25
[43]Gungabeesoon J,Tremblay ML,Uetani N.Localizing PRL-2 expression and determining the effects of dietary Mg2+on expression levels.Histochem Cell Biol,2016,146:99-111
[44]Uetani N,Hardy S,Gravel SP,et al.PRL2 links magnesium flux and sex-dependent circadian metabolic rhythms.JCIInsight,2017,2:e91722
[45]Pathak MK,Dhawan D,Lindner DJ,et al.Pentamidine is an inhibitor of PRL phosphatases with anticancer activity.Mol Cancer Ther,2002,1:1255-64
[46]Collaborators GMC.Global,regional,and national agesex specific mortality for 264 causes of death,1980-2016:a systematic analysis for the Global Burden of Disease Study 2016.Lancet,2017,390:1151-210
[47]Alonso A,Sasin J,Bottini N,et al.Protein tyrosine phosphatases in the human genome.Cell,2004,117:699-711
[48]Lin MD,Lee HT,Wang SC,et al.Expression of phosphatase of regenerating liver family genes during embryogenesis:an evolutionary developmental analysis among Drosophila,amphioxus,and zebrafish.BMC Dev Biol,2013,13:18
[49]Leitherer S,Clos J,Liebler-Tenorio EM,et al.Characterization of the protein tyrosine phosphatase LmPRL-1 secreted by Leishmania major via the exosome pathway.Infect Immun,2017,85:e00084-17
[50]Fagerberg L,Hallstrom BM,Oksvold P,et al.Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics.Mol Cell Proteomics,2014,13:397-406