title: Tumor suppressor Menin acts as a corepressor of LXRα to inhibit hepatic lipogenesis.
abstract: Menin, encoded by the MEN1 gene, was initially identified as a tumor suppressor for endocrine neoplasia. Our previous report showed that Menin enhances PPARα transactivity preventing triglyceride accumulation in the liver. Here, we further explore the role of Menin in liver steatosis. Transient transfection assays demonstrate that Menin inhibits the transcriptional activity of nuclear receptor liver X receptor α (LXRα). Accordingly, Menin overexpression results in reduced expression of LXRα target genes, such as lipogenic enzymes including SREBP-1c, FASN and SCD-1. Co-immunoprecipitation assays revealed physical interaction between Menin and LXRα. Collectively, our data suggest that Menin acts as a novel corepressor of LXRα and functions as a negative regulator of hepatic lipogenesis.
authors.affiliation: Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, People's Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Cheng
authors.affiliation: Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, People's Republic of China.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, Second Military Medical University, Shanghai 200433, People's Republic of China.
authors.forename: Sheng Sheng
authors.initials: SS
authors.lastname: Yang
authors.affiliation: Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, People's Republic of China.
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, People's Republic of China. Electronic address: jingang@sohu.com.
authors.forename: Gang
authors.initials: G
authors.lastname: Jin
authors.affiliation: Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, People's Republic of China. Electronic address: xuyu2006@medmail.com.cn.
authors.forename: Xu Yu
authors.initials: XY
authors.lastname: Zhou
authors.affiliation: Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, People's Republic of China.
authors.forename: Xian Gui
authors.initials: XG
authors.lastname: Hu
mesh_terms: D050156:Adipogenesis / Q000235:genetics*; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D015870:Gene Expression; D057809:HEK293 Cells; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D050155:Lipogenesis / Q000235:genetics; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000071518:Liver X Receptors; D008810:Mice, Inbred C57BL; D057093:Orphan Nuclear Receptors / Q000235:genetics* / Q000378:metabolism; D061251:Primary Cell Culture; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000071518:Liver X Receptors; C105373:MEN1 protein, human; C484898:Men1 protein, mouse; C000605213:NR1H3 protein, human; C000605214:Nr1h3 protein, mouse; D057093:Orphan Nuclear Receptors; D011518:Proto-Oncogene Proteins
keywords: Hepatic lipogenesis; Liver X receptor α; Menin