The antiobesity factor WDTC1 suppresses adipogenesis via the CRL4WDTC1 E3 ligase.
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.
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC, USA.
Beezly S
0000-0002-6969-9134
BS
Groh
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
Feng
0000-0002-7123-4475
F
Yan
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
Matthew D
0000-0003-1549-4915
MD
Smith
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC, USA.
Yanbao
Y
Yu
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC, USA.
Xian
X
Chen
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 yxiong@email.unc.edu.
Yue
0000-0003-2744-6566
Y
Xiong
D041721:3T3-L1 Cells; D050156:Adipogenesis / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D044842:Cullin Proteins / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D015870:Gene Expression; D057809:HEK293 Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D009154:Mutation; D010641:Phenotype; D011485:Protein Binding; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D013379:Substrate Specificity; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination; D053722:Receptors, Interleukin-17; D043743:Ubiquitin-Protein Ligase Complexes
D044842:Cullin Proteins; D004268:DNA-Binding Proteins; D006657:Histones; D011506:Proteins; D044767:Ubiquitin-Protein Ligases; C490415:Ddb1 protein, mouse; C408922:IL17RB protein, human; D053722:Receptors, Interleukin-17; C527990:Wdtc1 protein, mouse; D043743:Ubiquitin-Protein Ligase Complexes
WDTC1; adipose; adp; cullins; obesity