An E2F1-dependent gene expression program that determines the balance between proliferation and cell death.

ABSTRACT: The Rb/E2F pathway regulates the expression of genes essential for cell proliferation but that also trigger apoptosis. During normal proliferation, PI3K/Akt signaling blocks E2F1-induced apoptosis, thus serving to balance proliferation and death. We now identify a subset of E2F1 target genes that are specifically repressed by PI3K/Akt signaling, thus distinguishing the E2F1 proliferative or apoptotic function. RNAi-mediated inhibition of several of these PI3K-repressed E2F1 target genes, including AMPK alpha 2, impairs apoptotic induction by E2F1. Activation of AMPK alpha 2 with an AMP analog further stimulates E2F1-induced apoptosis. We also show that the presence of the E2F1 apoptotic expression program in breast and ovarian tumors coincides with good prognosis, emphasizing the importanc

SUBMITTER: Hallstrom TC 

PROVIDER: S-EPMC2243238 | biostudies-literature | 2008 Jan

REPOSITORIES: biostudies-literature