CDK9-mediated phosphorylation controls the interaction of TIP60 with the transcriptional machinery.

ABSTRACT: The acetyltransferase TIP60 is regulated by phosphorylation, and we have previously shown that phosphorylation of TIP60 on S86 by GSK-3 promotes p53-mediated induction of the BCL-2 protein PUMA. TIP60 phosphorylation by GSK-3 requires a priming phosphorylation on S90, and here, we identify CDK9 as a TIP60S90 kinase. We demonstrate that a phosphorylation-deficient mutant, TIP60^S90A, exhibits reduced interaction with chromatin, histone 3 and RNA Pol II, while its association with the TIP60 complex subunit EPC1 is not affected. Consistently, we find a diminished association of TIP60^S90A with the MYC gene. We show that cells expressing TIP60^S90A, but also TIP60^S86A, which retains S90 phosphorylation, exhibit reduced histone 4 acetylation and p

SUBMITTER: Brauns-Schubert P 

PROVIDER: S-EPMC5797957 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature