E3 ligase RCHY1 negatively regulates HDAC2

Biochem Biophys Res Commun. 2020 Jan 1;521(1):37-41. doi: 10.1016/j.bbrc.2019.10.049. Epub 2019 Oct 17.

Abstract

HDAC2, one of the class I histone deacetylase regulates epigenetic landscape through histone modification. Because HDAC2 is overexpressed in many cancers, cancer therapeutics against HDAC2 have been developed. Here we show novel mechanism of HDAC2 regulation by E3 ligase RCHY1. We found inverse correlation RCHY1 and HDAC2 levels in tumor tissue from six independent dataset using meta-analysis. Ectopic expression of RCHY1 decreased the level of HDAC2 from cancer cells including p53 wildtype, mutant and null cells. In addition, HDAC2 was increased by RCHY1 knockdown. RCHY1 directly interacts with HDAC2. Ectopic expression of wild type but not RING mutant RCHY1 increased HDAC2 levels. These data provide an evidence that RCHY1 negatively regulates HDAC2.

Keywords: HDAC2; Protein degradation; RCHY1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Histone Deacetylase 2 / genetics
  • Histone Deacetylase 2 / metabolism*
  • Humans
  • Mice
  • Mice, Nude
  • Ubiquitin-Protein Ligases / metabolism*

Substances

  • RCHY1 protein, human
  • Rchy1 protein, mouse
  • Ubiquitin-Protein Ligases
  • HDAC2 protein, human
  • Hdac2 protein, mouse
  • Histone Deacetylase 2