The antiobesity factor WDTC1 suppresses adipogenesis via the CRL4WDTC1 E3 ligase

EMBO Rep. 2016 May;17(5):638-47. doi: 10.15252/embr.201540500. Epub 2016 Apr 9.

Abstract

WDTC1/Adp encodes an evolutionarily conserved suppressor of lipid accumulation. While reduced WDTC1 expression is associated with obesity in mice and humans, its cellular function is unknown. Here, we demonstrate that WDTC1 is a component of a DDB1-CUL4-ROC1 (CRL4) E3 ligase. Using 3T3-L1 cell culture model of adipogenesis, we show that disrupting the interaction between WDTC1 and DDB1 leads to a loss of adipogenic suppression by WDTC1, increased triglyceride accumulation and adipogenic gene expression. We show that the CRL4(WDTC) (1) complex promotes histone H2AK119 monoubiquitylation, thus suggesting a role for this complex in transcriptional repression during adipogenesis. Our results identify a biochemical role for WDTC1 and extend the functional range of the CRL4 complex to the suppression of fat accumulation.

Keywords: WDTC1; adipose; adp; cullins; obesity.

MeSH terms

  • 3T3-L1 Cells
  • Adipogenesis* / genetics
  • Amino Acid Sequence
  • Animals
  • Cullin Proteins / genetics
  • Cullin Proteins / metabolism
  • DNA-Binding Proteins / metabolism
  • Gene Expression
  • HEK293 Cells
  • Histones / metabolism
  • Humans
  • Mice
  • Models, Molecular
  • Mutation
  • Phenotype
  • Protein Binding
  • Protein Conformation
  • Protein Interaction Domains and Motifs
  • Proteins / genetics
  • Proteins / metabolism*
  • RNA Interference
  • Substrate Specificity
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism*
  • Ubiquitination

Substances

  • Cullin Proteins
  • DNA-Binding Proteins
  • Ddb1 protein, mouse
  • Histones
  • IL17RB protein, human
  • Proteins
  • Wdtc1 protein, mouse
  • Ubiquitin-Protein Ligases