Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 279, Issue 52, Pages 54140-54152Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M410493200
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- NCI NIH HHS [R01 CA100848, CA100857, R01 CA100857, CA100848] Funding Source: Medline
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Genotoxic stress triggers apoptosis through multiple signaling pathways. Recent studies have demonstrated a specific induction of E2F1 accumulation and a role for E2F1 in apoptosis upon DNA damage. Induction of E2F1 is mediated by phosphorylation events that are dependent on DNA damage-responsive protein kinases, such as ATM. How ATM phosphorylation leads to E2F1 stabilization is unknown. We now show that 14-3-3tau, a phosphoserine-binding protein, mediates E2F1 stabilization. 14-3-3tau interacts with ATM-phosphorylated E2F1 during DNA damage and inhibits E2F1 ubiquitination. Depletion of 14-3-3tau or E2F1, but not E2F2 or E2F3, blocks adriamycin-induced apoptosis. 14-3-3tau is also required for expression and induction of E2F1 apoptotic targets, such as p73, Apaf-1, and caspases, during DNA damage. Together, these data demonstrate a novel function for 14-3-3tau in the regulation of E2F1 protein stability and apoptosis during DNA damage.
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