title: Role of suppressor of cytokine signaling 3 in lipid metabolism: analysis based on a phage-display human liver cDNA library.
abstract: Suppressor of cytokine signaling 3 (SOCS3) is a likely mediator of feedback inhibition on the leptin receptor and may cause physiological leptin-resistance, leading to the development of obesity. The aim of this study was to identify potential peptides interacting with purified SOCS3 by using a phage-display human liver cDNA library. We developed a T7 select phage-display system with purified SOCS3 as bait to screen a human liver cDNA library. After 4 rounds of screening and sequencing analysis, we found that phage-presenting peptide RGGVVTSNPLGF show significant binding to SOCS3. The peptide sequence was similar to the sequence of amino acids 644-655 of C-terminal extra-polypeptide of very-long-chain acyl-CoA dehydrogenase (VLCAD), which is 1 of 4 flavoproteins that catalyzing the initial step of the mitochondrial fatty acid β-oxidation, implying a close relationship between SOCS3 and VLCAD. We identified VLCAD as a novel SOCS3 interacting protein both in vitro and vivo, and found that SOCS3 mediates the ubiquitination pathway for proteasomal degradation of VLCAD C-terminal extra-polypeptide via its SOCS-box. Animal experimentation demonstrated that VLCAD is functionally involved in SOCS3 binding and thus, SOCS3 play an important role in the regulation of fatty acid β-oxidation. In conclusion, SOCS3 is an important factor for lipid metabolism and a potential drug-target for treatment of widespread obesity.
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Luo
authors.forename: Tingting
authors.initials: T
authors.lastname: Zou
authors.forename: Nan
authors.initials: N
authors.lastname: Lu
authors.forename: Fan
authors.initials: F
authors.lastname: Chai
authors.forename: Xing
authors.initials: X
authors.lastname: Ye
authors.forename: YeFu
authors.initials: Y
authors.lastname: Wang
authors.forename: Yipeng
authors.initials: Y
authors.lastname: Qi
mesh_terms: D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D005227:Fatty Acids / Q000378:metabolism; D015723:Gene Library; D006801:Humans; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D019151:Peptide Library; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D005227:Fatty Acids; D019151:Peptide Library; C106644:SOCS3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D044942:Acyl-CoA Dehydrogenase, Long-Chain