Journal
EMBO REPORTS
Volume 17, Issue 5, Pages 638-647Publisher
WILEY-BLACKWELL
DOI: 10.15252/embr.201540500
Keywords
adipose; adp; cullins; obesity; WDTC1
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Funding
- U.S. National Institutes of Health [NCI CPTAC 1U24CA160035, R01-GM067113]
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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(WDTC1) 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.
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