RUNX3 modulates DNA damage-mediated phosphorylation of tumor suppressor p53 at Ser-15 and acts as a co-activator for p53.

ABSTRACT: Although it has been shown that the gastric tumor suppressor RUNX3 has a growth inhibitory activity, the precise molecular mechanisms behind RUNX3-mediated tumor suppression remained unclear. In this study, we found that RUNX3 is closely involved in DNA damage-dependent phosphorylation of tumor suppressor p53 at Ser-15 and acts as a co-activator for p53. The small interference RNA-mediated knockdown of RUNX3 inhibited adriamycin (ADR)-dependent apoptosis in p53-proficient cells but not in p53-deficient cells in association with a significant reduction of p53-target gene expression as well as phosphorylation of p53 at Ser-15. In response to ADR, RUNX3 was induced to accumulate in the cell nucleus and co-localized with p53. Immunoprecipitation experiments demonstrated that RUNX3 forms a comp

SUBMITTER: Yamada C 

PROVIDER: S-EPMC2878082 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature