The antiobesity factor WDTC1 suppresses adipogenesis via the CRL4WDTC1 E3 ligase

BS Groh, F Yan, MD Smith, Y Yu, X Chen, Y Xiong - EMBO reports, 2016 - embopress.org
BS Groh, F Yan, MD Smith, Y Yu, X Chen, Y Xiong
EMBO reports, 2016embopress.org
WDTC 1/Adp encodes an evolutionarily conserved suppressor of lipid accumulation. While
reduced WDTC 1 expression is associated with obesity in mice and humans, its cellular
function is unknown. Here, we demonstrate that WDTC 1 is a component of a DDB 1‐CUL 4‐
ROC 1 (CRL 4) E3 ligase. Using 3T3‐L1 cell culture model of adipogenesis, we show that
disrupting the interaction between WDTC 1 and DDB 1 leads to a loss of adipogenic
suppression by WDTC 1, increased triglyceride accumulation and adipogenic gene …
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 CRL4WDTC1 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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