Dimerization-driven degradation of C. elegans and human E proteins

Genes Dev. 2015 Jul 1;29(13):1356-61. doi: 10.1101/gad.261917.115.

Abstract

E proteins are conserved regulators of growth and development. We show that the Caenorhabditis elegans E-protein helix-loop-helix-2 (HLH-2) functions as a homodimer in directing development and function of the anchor cell (AC) of the gonad, the critical organizer of uterine and vulval development. Our structure-function analysis of HLH-2 indicates that dimerization drives its degradation in other uterine cells (ventral uterine precursor cells [VUs]) that initially have potential to be the AC. We also provide evidence that this mode of dimerization-driven down-regulation can target other basic HLH (bHLH) dimers as well. Remarkably, human E proteins can functionally substitute for C. elegans HLH-2 in regulating AC development and also display dimerization-dependent degradation in VUs. Our results suggest that dimerization-driven regulation of bHLH protein stability may be a conserved mechanism for differential regulation in specific cell contexts.

Keywords: C. elegans; E2A; HLH-2; TCF3; bHLH.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics*
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Caenorhabditis elegans / embryology
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • Cells, Cultured
  • Dimerization
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Developmental*
  • Humans
  • Protein Processing, Post-Translational*
  • Protein Stability
  • Proteolysis*
  • Uterus / embryology

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Caenorhabditis elegans Proteins