FOXO3/FKHRL1 is activated by 5-aza-2-deoxycytidine and induces silenced caspase-8 in neuroblastoma.

ABSTRACT: Forkhead box O (FOXO) transcription factors control diverse cellular functions, such as cell death, metabolism, and longevity. We analyzed FOXO3/FKHRL1 expression and subcellular localization in tumor sections of neuroblastoma patients and observed a correlation between nuclear FOXO3 and high caspase-8 expression. In neuroblastoma caspase-8 is frequently silenced by DNA methylation. Conditional FOXO3 activated caspase-8 gene expression but did not change the DNA-methylation pattern of regulatory sequences in the caspase-8 gene. Instead, FOXO3 induced phosphorylation of its binding partner ATM and of the ATM downstream target cAMP-responsive element binding protein (CREB), which was critical for FOXO3-mediated caspase-8 expression. Caspase-8 levels above a critical threshold sensitized neur

SUBMITTER: Geiger K 

PROVIDER: S-EPMC3364184 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature