The SUMO pathway promotes basic helix-loop-helix proneural factor activity via a direct effect on the Zn finger protein senseless

Mol Cell Biol. 2012 Jul;32(14):2849-60. doi: 10.1128/MCB.06595-11. Epub 2012 May 14.

Abstract

During development, proneural transcription factors of the basic helix-loop-helix (bHLH) family are required to commit cells to a neural fate. In Drosophila neurogenesis, a key mechanism promoting sense organ precursor (SOP) fate is the synergy between proneural factors and their coactivator Senseless in transcriptional activation of target genes. Here we present evidence that posttranslational modification by SUMO enhances this synergy via an effect on Senseless protein. We show that Senseless is a direct target for SUMO modification and that mutagenesis of a predicted SUMOylation motif in Senseless reduces Senseless/proneural synergy both in vivo and in cell culture. We propose that SUMOylation of Senseless via lysine 509 promotes its synergy with proneural proteins during transcriptional activation and hence regulates an important step in neurogenesis leading to the formation and maturation of the SOPs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Animals
  • Animals, Genetically Modified
  • Base Sequence
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Cell Line
  • DNA Primers / genetics
  • Drosophila / genetics
  • Drosophila / growth & development
  • Drosophila / metabolism*
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Genes, Insect
  • HeLa Cells
  • Humans
  • Lysine / chemistry
  • Models, Neurological
  • Mutagenesis, Site-Directed
  • Neurogenesis / genetics
  • Neurogenesis / physiology
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Sense Organs / growth & development
  • Sense Organs / metabolism
  • Small Ubiquitin-Related Modifier Proteins / genetics
  • Small Ubiquitin-Related Modifier Proteins / metabolism*
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Two-Hybrid System Techniques

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • DNA Primers
  • Drosophila Proteins
  • Nuclear Proteins
  • Recombinant Fusion Proteins
  • Small Ubiquitin-Related Modifier Proteins
  • Transcription Factors
  • sens protein, Drosophila
  • Lysine