title: Polo-like kinase 1 inhibits the activity of positive transcription elongation factor of RNA Pol II b (P-TEFb).
abstract: Polo-like kinase 1 (Plk1) is a highly conserved Ser/Thr kinase in eukaryotes and plays a critical role in various aspects of the cell cycle. Plk1 exerts its multiple functions by phosphorylating its substrates. In this study, we found that Plk1 can interact with cyclin T1/Cdk9 complex-the main form of the positive transcription elongation complex b (P-TEFb), and its C-terminal polo-box domain is responsible for the binding. Further analysis indicated that Plk1 could phosphorylate cyclin T1 at Ser564 and inhibit the kinase activity of cyclin T1/Cdk9 complex on phosphorylation of the C-terminal domain (CTD) of RNA polymerase II. By taking the approach of luciferase assay, we demonstrated that over-expression of both wild type Plk1 and constitutively active form of Plk1 inhibits the P-TEFb dependent HIV-1 LTR transcription, while knockdown of Plk1 increases the HIV-1 LTR transcription. Consistently, the data from the HIV-1 pseudovirus reporter assay indicated that Plk1 blocks the gene expression of HIV-1 pseudovirus. Taken together, our results revealed that Plk1 negatively regulates the RNA polymerase II-dependent transcription through inhibiting the activity of cyclin T1/Cdk9 complex.
authors: Center for Molecular Immunology, CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, PR China.
authors: Liangzhen
authors: L
authors: Jiang
authors: Yan
authors: Y
authors: Huang
authors: Min
authors: M
authors: Deng
authors: Ting
authors: T
authors: Liu
authors: Wenbin
authors: W
authors: Lai
authors: Xin
authors: X
authors: Ye
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D056906:Cyclin T / Q000235:genetics / Q000378:metabolism; D042863:Cyclin-Dependent Kinase 9 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D042925:Positive Transcriptional Elongation Factor B / Q000235:genetics* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D012319:RNA Polymerase II / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D016865:Reassortant Viruses / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic; D018116:Vesiculovirus / Q000235:genetics / Q000378:metabolism; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D056906:Cyclin T; D042863:Cyclin-Dependent Kinase 9; D008156:Luciferases; D042925:Positive Transcriptional Elongation Factor B; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D012319:RNA Polymerase II; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D000097869:Polo-Like Kinase 1; C503684:CCNT1 protein, human; C467969:CDK9 protein, human
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