P38 MAPK- and Akt-mediated p300 phosphorylation regulates its degradation to facilitate nucleotide excision repair.

ABSTRACT: Besides the primary histone acetyltransferase (HAT)-mediated chromatin remodeling function, co-transcriptional factor, p300, is also known to play a distinct role in DNA repair. However, the exact mechanism of p300 function in DNA repair has remained unclear and difficult to discern due to the phosphorylation and degradation of p300 in response to DNA damage. Here, we have demonstrated that p300 is only degraded in the presence of specific DNA lesions, which are the substrates of nucleotide excision repair (NER) pathway. In contrast, DNA double-strand breaks fail to degrade p300. Degradation is initiated by phosphorylation of p300 at serine 1834, which is catalyzed by the cooperative action of p38 mitogen-activated protein kinases and Akt kinases. In depth, functional analysis revealed tha

SUBMITTER: Wang QE 

PROVIDER: S-EPMC3561975 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature