KRAB-type zinc-finger protein Apak specifically regulates p53-dependent apoptosis.

Only a few p53 regulators have been shown to participate in the selective control of p53-mediated cell cycle arrest or apoptosis. How p53-mediated apoptosis is negatively regulated remains largely unclear. Here we report that Apak (ATM and p53-associated KZNF protein), a Krueppel-associated box (KRAB)-type zinc-finger protein, binds directly to p53 ...
in unstressed cells, specifically downregulates pro-apoptotic genes, and suppresses p53-mediated apoptosis by recruiting KRAB-box-associated protein (KAP)-1 and histone deacetylase 1 (HDAC1) to attenuate the acetylation of p53. Apak inhibits p53 activity by interacting with ATM, a previously identified p53 activator. In response to stress, Apak is phosphorylated by ATM and dissociates from p53, resulting in activation of p53 and induction of apoptosis. These findings revealed Apak to be a negative regulator of p53-mediated apoptosis and showed the dual role of ATM in p53 regulation.
Mesh Terms:
Acetylation, Amino Acid Sequence, Apoptosis, Apoptosis Regulatory Proteins, Binding Sites, Carrier Proteins, Cell Cycle Proteins, Cell Line, Tumor, DNA Damage, DNA-Binding Proteins, Gene Expression, Histone Deacetylase 1, Histone Deacetylases, Humans, Models, Biological, Molecular Sequence Data, Phosphorylation, Protein Binding, Protein Interaction Domains and Motifs, Protein-Serine-Threonine Kinases, RNA Interference, Repressor Proteins, Serine, Tumor Suppressor Protein p53, Tumor Suppressor Proteins, Two-Hybrid System Techniques, Zinc Fingers, bcl-2-Associated X Protein
Nat. Cell Biol.
Date: May. 01, 2009
Download Curated Data For This Publication
109328
Switch View:
  • Interactions 4