TRIM24 mediates the interaction of the retinoic acid receptor alpha with the proteasome

FEBS Lett. 2018 Apr;592(8):1426-1433. doi: 10.1002/1873-3468.13033. Epub 2018 Mar 30.

Abstract

The nuclear retinoic acid (RA) receptors (RARα, β and γ) are ligand-dependent regulators of transcription. Upon activation by RA, they are recruited at the promoters of target genes together with several coregulators. Then, they are degraded by the ubiquitin proteasome system. Here, we report that the degradation of the RARα subtype involves ubiquitination and the tripartite motif protein TRIM24, which was originally identified as a ligand-dependent corepressor of RARα. We show that in response to RA, TRIM24 serves as an adapter linking RARα to the proteasome for its degradation. In addition, TRIM24 and the proteasome are recruited with RARα to the promoters of target genes and thus are inherently linked to RARα transcriptional activity.

Keywords: TRIM24; degradation; proteasome; retinoic acid receptor; transcription; ubiquitin.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • HeLa Cells
  • Humans
  • MCF-7 Cells
  • Proteasome Endopeptidase Complex / genetics
  • Proteasome Endopeptidase Complex / metabolism*
  • Proteolysis*
  • Retinoic Acid Receptor alpha / genetics
  • Retinoic Acid Receptor alpha / metabolism*
  • Tretinoin / pharmacology
  • Ubiquitination / drug effects
  • Ubiquitination / physiology*

Substances

  • Carrier Proteins
  • Retinoic Acid Receptor alpha
  • TRIM24 protein, human
  • Tretinoin
  • Proteasome Endopeptidase Complex