Groh Beezly S, Yan Feng, Smith Matthew D, Yu Yanbao, Chen Xian, Xiong Yue
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC, USA.
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
EMBO Rep. 2016 May;17(5):638-47. doi: 10.15252/embr.201540500. Epub 2016 Apr 9.
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.
WDTC1/Adp编码一种在进化上保守的脂质积累抑制因子。虽然WDTC1表达降低与小鼠和人类的肥胖有关,但其细胞功能尚不清楚。在这里,我们证明WDTC1是DDB1-CUL4-ROC1(CRL4)E3泛素连接酶的一个组成部分。使用3T3-L1细胞脂肪生成培养模型,我们发现破坏WDTC1与DDB1之间的相互作用会导致WDTC1失去对脂肪生成的抑制作用,甘油三酯积累增加以及脂肪生成基因表达增加。我们表明CRL4(WDTC)(1)复合物促进组蛋白H2AK119单泛素化,从而表明该复合物在脂肪生成过程中的转录抑制中发挥作用。我们的结果确定了WDTC1的生化作用,并将CRL4复合物的功能范围扩展到脂肪积累的抑制。