Apak competes with p53 for direct binding to intron 1 of p53AIP1 to regulate apoptosis

EMBO Rep. 2012 Apr;13(4):363-70. doi: 10.1038/embor.2012.10.

Abstract

The KRAB-type zinc-finger protein Apak was recently identified as a negative regulator of p53-mediated apoptosis. However, the mechanism of this selective regulation is not fully understood. Here, we show that Apak recognizes the TCTTN2−30TTGT consensus sequence through its zinc-fingers. This sequence is specifically found in intron 1 of the proapoptotic p53 target gene p53AIP1 and largely overlaps with the p53-binding sequence. Apak competes with p53 for binding to this site to inhibit p53AIP1 expression. Upon DNA damage, Apak dissociates from the DNA, which abolishes its inhibitory effect on p53-mediated apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis Regulatory Proteins / genetics*
  • Apoptosis Regulatory Proteins / metabolism*
  • Apoptosis*
  • Base Sequence
  • Binding, Competitive*
  • DNA Damage
  • DNA-Binding Proteins / metabolism*
  • HCT116 Cells
  • Humans
  • Introns / genetics*
  • Molecular Sequence Data
  • Protein Binding
  • Repressor Proteins / metabolism
  • Transcription, Genetic
  • Tumor Suppressor Protein p53 / metabolism*
  • Zinc Fingers

Substances

  • Apoptosis Regulatory Proteins
  • DNA-Binding Proteins
  • P53AIP1 protein, human
  • Repressor Proteins
  • Tumor Suppressor Protein p53
  • ZNF420 protein, human