Mechanistic differences in the transcriptional activation of p53 by 14-3-3 isoforms.

ABSTRACT: p53 maintains genome integrity by initiating the transcription of genes involved in cell-cycle arrest, senescence, apoptosis and DNA repair. The activity of p53 is regulated by both post-translational modifications and protein-protein interactions. p53 that has been phosphorylated at S366, S378 and T387 binds 14-3-3 proteins in vitro. Here, we show that these sites are potential 14-3-3 binding sites in vivo. Epsilon (epsilon) and gamma (gamma) isoforms required phosphorylation at either of these sites for efficient interaction with p53, while for sigma (sigma) and tau (tau) these sites are dispensable. Further, sigma and tau bound more weakly to p53 C-terminal phosphopeptides than did epsilon and gamma. However, the four isoforms bound tightly to di-phosphorylated p53 C-terminal peptides t

SUBMITTER: Rajagopalan S 

PROVIDER: S-EPMC2817464 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature