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.