Yin-Yang strands of PCAF/Hedgehog axis in cancer control

Trends Mol Med. 2014 Aug;20(8):416-8. doi: 10.1016/j.molmed.2014.05.003. Epub 2014 Jun 4.

Abstract

PCAF (p300/CBP associated factor) harbors acetyltransferase and a recently identified ubiquitylation activity that regulates gene expression in response to genotoxic stress or mitogenic signals. We highlight the dual role of PCAF in the control of Hedgehog signaling, a master regulator of tissue development, stemness, and tumorigenesis. By promoting histone acetylation at Hedgehog/GLI1 target gene promoters or direct ubiquitylation and proteolysis of GLI1, the PCAF/GLI1 axis stands as a promising therapeutic target for Hedgehog-dependent tumors.

Keywords: E3-ubiquitin ligase; Hedgehog; PCAF; acetyltransferase; cancer; p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyltransferases / metabolism
  • Animals
  • Drug Discovery
  • Hedgehog Proteins / metabolism*
  • Humans
  • Molecular Targeted Therapy
  • Neoplasms / drug therapy
  • Neoplasms / metabolism*
  • Signal Transduction* / drug effects
  • Tumor Suppressor Protein p53 / metabolism
  • Ubiquitination
  • p300-CBP Transcription Factors / metabolism*

Substances

  • Hedgehog Proteins
  • Tumor Suppressor Protein p53
  • Acetyltransferases
  • p300-CBP Transcription Factors
  • p300-CBP-associated factor