Objective:PCBP1 is a family member of heterogeneous nuclear ribonucleoproteins (hnRNPs) that belong to RNA-binding proteins and bear three KH domains. The protein plays a pivotal role in post-transcriptional regulatio...Objective:PCBP1 is a family member of heterogeneous nuclear ribonucleoproteins (hnRNPs) that belong to RNA-binding proteins and bear three KH domains. The protein plays a pivotal role in post-transcriptional regulation for RNA metabolism and RNA function in gene expression. We hypothesized and were going to identify that the regulatory function of PCBP1 is performed through different complexes of proteins that include PCBP1. Methods:To test our hypothesis,approaches of protein wal-king with a yeast two-hybrid system (Y2H),pulling down in yeasts,co-immunoprecipitation and immunofluorescent microscopy assay were employed in this study. The PCBP1 was used as the initial "walker" to search for its interaction partner(s). Results:Candidate proteins including MYL6,PECAM1,CSH1,RAB7,p57KIP2,ACTG1,RBMS1 and PSG4-like were identified with selection mediums and preceding methods. Conclusion:With these candidate protein molecules,some protein complexes associating with PCBP1 are proposed,which may help in a better understanding of physiological functions of PCBP1 and proved evidence that PCBP1 is involved in variant biological pathways.展开更多
Objective To screen the proteins associated with four-and-a-half LIM domains 3(FHL3) 3' untranslated region(3'UTR) in glioma cells. Methods Western blot was adopted to detect the regulatory effect of poly(C)-b...Objective To screen the proteins associated with four-and-a-half LIM domains 3(FHL3) 3' untranslated region(3'UTR) in glioma cells. Methods Western blot was adopted to detect the regulatory effect of poly(C)-binding protein 2(PCBP2) on FHL3. Biotin pull-down and sliver staining were employed to screen and verify the candidate binding proteins of FHL3 3'UTR. Then liquid chromatography-tandem mass spectrometry(LC-MS/MS) and molecule annotation system were used to identify and analyze the candidate binding proteins. Immunoprecipitation was conducted to study the interaction between PCBP2 and polypyrimidine tract-binding protein 1(PTBP1), a binding protein identified by LC-MS/MS. Results PCBP2 could bind to FHL3 mRNA 3'UTR-A and inhibited the expression of FHL3 in T98 G glioms cells. 22 candidate binding proteins were identified. Among them, there were 11 RNA binding proteins, including PCBP2. PTBP1 associated with FHL3 mRNA 3'UTR and interacted with PCBP2 protein. Conclusion PCBP2 and PTBP1 can both associate with FHL3 mRNA 3'UTR through forming a protein complex.展开更多
[目的]研究多聚胞嘧啶结合蛋白-1(poly(C)-binding protein 1,PCBP1)在结直肠癌(colorectal cancer,CRC)组织中的表达及其临床意义。[方法 ]采用免疫组织化学技术(EnVision法)检测140例CRC组织及相对应140例癌旁肠黏膜组织中PCBP1的表...[目的]研究多聚胞嘧啶结合蛋白-1(poly(C)-binding protein 1,PCBP1)在结直肠癌(colorectal cancer,CRC)组织中的表达及其临床意义。[方法 ]采用免疫组织化学技术(EnVision法)检测140例CRC组织及相对应140例癌旁肠黏膜组织中PCBP1的表达情况,使用卡方检验分析PCBP1的表达与CRC患者的临床病理参数之间的关系,Kaplan-Meier生存曲线分析及Cox多因素分析PCBP1的表达对CRC患者预后的影响。[结果]PCBP1在CRC组织的阳性率为37.1%(52/140),明显低于癌旁结直肠组织的52.1%(73/140);PCBP1的表达情况与肿瘤TNM分期及淋巴结转移相关;Cox多因素回归分析结果显示,PCBP1表达、TNM分期及术后辅助治疗与CRC的预后相关;Kaplan-Meier生存曲线结果表明PCBP1低表达的病例预后较高表达的病例差,差异具有统计学意义(P=0.001)。[结论]PCBP1在CRC组织中低表达,其表达失调与CRC的发生、发展及预后有密切关系。展开更多
Maintenance of cellular homeostasis and genome integrity is a critical responsibility of DNA double-strand break(DSB)signaling.P53-binding protein 1(53BP1)plays a critical role in coordinating the DSB repair pathway c...Maintenance of cellular homeostasis and genome integrity is a critical responsibility of DNA double-strand break(DSB)signaling.P53-binding protein 1(53BP1)plays a critical role in coordinating the DSB repair pathway choice and promotes the non-homologous end-joining(NHEJ)-mediated DSB repair pathway that rejoins DSB ends.New insights have been gained into a basic molecular mechanism that is involved in 53BP1 recruitment to the DNA lesion and how 53BP1 then recruits the DNA break-responsive effectors that promote NHEJ-mediated DSB repair while inhibiting homologous recombination(HR)signaling.This review focuses on the up-and downstream pathways of 53BP1 and how 53BP1 promotes NHEJ-mediated DSB repair,which in turn promotes the sensitivity of poly(ADP-ribose)polymerase inhibitor(PARPi)in BRCA1-deficient cancers and consequently provides an avenue for improving cancer therapy strategies.展开更多
基金Supported in part by the “985” program(985-2-035-39) of the Chinese Ministry of Education“973” project(2007CB511902)of the Chinese Ministry of Sciences and Technology+1 种基金National Nature Science Foundation(30671157)the NewYork State Office of Mental Retardation and Developmental Disabilities(NYSOMRDD)~~
文摘Objective:PCBP1 is a family member of heterogeneous nuclear ribonucleoproteins (hnRNPs) that belong to RNA-binding proteins and bear three KH domains. The protein plays a pivotal role in post-transcriptional regulation for RNA metabolism and RNA function in gene expression. We hypothesized and were going to identify that the regulatory function of PCBP1 is performed through different complexes of proteins that include PCBP1. Methods:To test our hypothesis,approaches of protein wal-king with a yeast two-hybrid system (Y2H),pulling down in yeasts,co-immunoprecipitation and immunofluorescent microscopy assay were employed in this study. The PCBP1 was used as the initial "walker" to search for its interaction partner(s). Results:Candidate proteins including MYL6,PECAM1,CSH1,RAB7,p57KIP2,ACTG1,RBMS1 and PSG4-like were identified with selection mediums and preceding methods. Conclusion:With these candidate protein molecules,some protein complexes associating with PCBP1 are proposed,which may help in a better understanding of physiological functions of PCBP1 and proved evidence that PCBP1 is involved in variant biological pathways.
基金Supported by Peking Union Medical College Youth Fundthe Fundamental Research Funds for the Central Universities(3332013052)
文摘Objective To screen the proteins associated with four-and-a-half LIM domains 3(FHL3) 3' untranslated region(3'UTR) in glioma cells. Methods Western blot was adopted to detect the regulatory effect of poly(C)-binding protein 2(PCBP2) on FHL3. Biotin pull-down and sliver staining were employed to screen and verify the candidate binding proteins of FHL3 3'UTR. Then liquid chromatography-tandem mass spectrometry(LC-MS/MS) and molecule annotation system were used to identify and analyze the candidate binding proteins. Immunoprecipitation was conducted to study the interaction between PCBP2 and polypyrimidine tract-binding protein 1(PTBP1), a binding protein identified by LC-MS/MS. Results PCBP2 could bind to FHL3 mRNA 3'UTR-A and inhibited the expression of FHL3 in T98 G glioms cells. 22 candidate binding proteins were identified. Among them, there were 11 RNA binding proteins, including PCBP2. PTBP1 associated with FHL3 mRNA 3'UTR and interacted with PCBP2 protein. Conclusion PCBP2 and PTBP1 can both associate with FHL3 mRNA 3'UTR through forming a protein complex.
文摘[目的]研究多聚胞嘧啶结合蛋白-1(poly(C)-binding protein 1,PCBP1)在结直肠癌(colorectal cancer,CRC)组织中的表达及其临床意义。[方法 ]采用免疫组织化学技术(EnVision法)检测140例CRC组织及相对应140例癌旁肠黏膜组织中PCBP1的表达情况,使用卡方检验分析PCBP1的表达与CRC患者的临床病理参数之间的关系,Kaplan-Meier生存曲线分析及Cox多因素分析PCBP1的表达对CRC患者预后的影响。[结果]PCBP1在CRC组织的阳性率为37.1%(52/140),明显低于癌旁结直肠组织的52.1%(73/140);PCBP1的表达情况与肿瘤TNM分期及淋巴结转移相关;Cox多因素回归分析结果显示,PCBP1表达、TNM分期及术后辅助治疗与CRC的预后相关;Kaplan-Meier生存曲线结果表明PCBP1低表达的病例预后较高表达的病例差,差异具有统计学意义(P=0.001)。[结论]PCBP1在CRC组织中低表达,其表达失调与CRC的发生、发展及预后有密切关系。
文摘Maintenance of cellular homeostasis and genome integrity is a critical responsibility of DNA double-strand break(DSB)signaling.P53-binding protein 1(53BP1)plays a critical role in coordinating the DSB repair pathway choice and promotes the non-homologous end-joining(NHEJ)-mediated DSB repair pathway that rejoins DSB ends.New insights have been gained into a basic molecular mechanism that is involved in 53BP1 recruitment to the DNA lesion and how 53BP1 then recruits the DNA break-responsive effectors that promote NHEJ-mediated DSB repair while inhibiting homologous recombination(HR)signaling.This review focuses on the up-and downstream pathways of 53BP1 and how 53BP1 promotes NHEJ-mediated DSB repair,which in turn promotes the sensitivity of poly(ADP-ribose)polymerase inhibitor(PARPi)in BRCA1-deficient cancers and consequently provides an avenue for improving cancer therapy strategies.