A role for 14-3-3 tau in E2F1 stabilization and DNA damage-induced apoptosis.

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 14-3-3 tau, a phosphoserine-binding protein, mediates E2F1 stabilization. 14-3-3 tau interacts with ATM-phosphorylated E2F1 during DNA damage and inhibits E2F1 ubiquitination. Depletion of 14-3-3 tau or E2F1, but not E2F2 or E2F3, blocks adriamycin-induced apoptosis. 14-3-3 tau 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 14-3-3 tau in the regulation of E2F1 protein stability and apoptosis during DNA damage.
Mesh Terms:
14-3-3 Proteins, Apoptosis, Cell Cycle Proteins, Cell Line, DNA Damage, DNA-Binding Proteins, Doxorubicin, Drug Stability, E2F Transcription Factors, E2F1 Transcription Factor, E2F3 Transcription Factor, Enzyme Activation, Enzyme-Linked Immunosorbent Assay, Glutathione Transferase, Green Fluorescent Proteins, Phosphorylation, Protein-Serine-Threonine Kinases, Recombinant Fusion Proteins, Reverse Transcriptase Polymerase Chain Reaction, Transcription Factors, Transfection, Tumor Suppressor Proteins, Two-Hybrid System Techniques, Ubiquitin
J. Biol. Chem.
Date: Dec. 24, 2004
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