Unknown

Dataset Information

0

PKC phosphorylates HEXIM1 and regulates P-TEFb activity.


ABSTRACT: The positive transcription elongation factor b (P-TEFb) regulates RNA polymerase II elongation. In cells, P-TEFb partitions between small active and larger inactive states. In the latter, HEXIM1 binds to 7SK snRNA and recruits as well as inactivates P-TEFb in the 7SK snRNP. Several stimuli can affect this P-TEFb equilibrium. In this study, we demonstrate that protein kinase C (PKC) phosphorylates the serine at position158 (S158) in HEXIM1. This phosphorylated HEXIM1 protein neither binds to 7SK snRNA nor inhibits P-TEFb. Phorbol esters or the engagement of the T cell antigen receptor, which activate PKC and the expression of the constitutively active (CA) PKC? protein, which is found in T cells, inhibit the formation of the 7SK snRNP. All these stimuli increase P-TEFb-dependent transcription. In contrast, the kinase-negative PKC? and the mutant HEXIM1 (S158A) proteins block effects of these PKC-activating stimuli. These results indicate that the phosphorylation of HEXIM1 by PKC represents a major regulatory step of P-TEFb activity in cells.

SUBMITTER: Fujinaga K 

PROVIDER: S-EPMC3467075 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

altmetric image

Publications

PKC phosphorylates HEXIM1 and regulates P-TEFb activity.

Fujinaga Koh K   Barboric Matjaz M   Li Qintong Q   Luo Zeping Z   Price David H DH   Peterlin B Matija BM  

Nucleic acids research 20120720 18


The positive transcription elongation factor b (P-TEFb) regulates RNA polymerase II elongation. In cells, P-TEFb partitions between small active and larger inactive states. In the latter, HEXIM1 binds to 7SK snRNA and recruits as well as inactivates P-TEFb in the 7SK snRNP. Several stimuli can affect this P-TEFb equilibrium. In this study, we demonstrate that protein kinase C (PKC) phosphorylates the serine at position158 (S158) in HEXIM1. This phosphorylated HEXIM1 protein neither binds to 7SK  ...[more]

Similar Datasets

| S-EPMC7525814 | biostudies-literature
| S-EPMC2831806 | biostudies-literature
| S-EPMC5111705 | biostudies-literature
| S-EPMC1356324 | biostudies-literature
| S-EPMC2014796 | biostudies-literature
| S-EPMC6838758 | biostudies-literature
| S-EPMC2651907 | biostudies-literature
| S-EPMC4132729 | biostudies-literature
| S-EPMC2168891 | biostudies-literature
| S-EPMC1955226 | biostudies-literature