Small ubiquitin-like modifier (SUMO) protein-specific protease 1 de-SUMOylates Sharp-1 protein and controls adipocyte differentiation

J Biol Chem. 2014 Aug 8;289(32):22358-64. doi: 10.1074/jbc.M114.571950. Epub 2014 Jun 18.


Adipocyte differentiation is regulated by a transcriptional cascade that mainly includes CCAAT/enhancer-binding protein family members and the nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ). Here we show the defects in adipocyte differentiation as well as PPARγ expression in Senp1(-/-) mouse embryonic fibroblast cells induced by adipogenic stimuli. We further determine that SENP1 is a specific de-SUMOylation protease for Sharp-1, a repressor for PPARγ transcription and adipogenesis. SENP1 enhances adipogenesis through de-SUMOylation of Sharp-1, which then releases Sharp-1 repression of PPARγ expression and adipocyte differentiation. These results reveal SENP1 as a novel regulator in adipogenesis.

Keywords: Adipogenesis; Cell Differentiation; Gene Transcription; Peroxisome Proliferator-activated Receptor (PPAR); SUMOylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / cytology*
  • Adipocytes / metabolism*
  • Adipogenesis / physiology
  • Animals
  • Cell Differentiation / physiology
  • Cells, Cultured
  • Cysteine Endopeptidases
  • Endopeptidases / deficiency
  • Endopeptidases / genetics
  • Endopeptidases / metabolism*
  • Gene Expression Regulation
  • Mice
  • Mice, Knockout
  • Mutagenesis, Site-Directed
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • Small Ubiquitin-Related Modifier Proteins / metabolism
  • Sumoylation
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*


  • Bhlhb3 protein, mouse
  • PPAR gamma
  • Small Ubiquitin-Related Modifier Proteins
  • Transcription Factors
  • Endopeptidases
  • Cysteine Endopeptidases
  • Senp1 protein, mouse