ATM regulates a RASSF1A-dependent DNA damage response.

ABSTRACT: Hypermethylation of CpG islands in the RASSF1 promoter is one of the most frequent events identified in human cancer. The epigenetic-driven loss of RASSF1A protein expression is observed more often in tumors of higher grade and correlates with a decreased responsiveness to DNA-damaging therapy. Ras association domain-containing family 1A (RASSF1A) promotes apoptosis by signaling through the MST2 and LATS1 kinases, leading to stabilization of the YAP1/p73 transcriptional complex. Here we provide evidence for a new pathway linking DNA damage signaling to RASSF1A via the main sensor of double-strand breaks in cells, ataxia telangiectasia mutated (ATM). We show that, upon DNA damage, RASSF1A is phosphorylated by ATM on Ser131 and is involved in the activation of both MST2 and LATS1, leading to

SUBMITTER: Hamilton G 

PROVIDER: S-EPMC4861209 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature