title: Lactacystin inhibits 3T3-L1 adipocyte differentiation through induction of CHOP-10 expression.
abstract: Hormonal induction triggers a cascade leading to the expression of CCAAT/enhancer-binding protein(C/EBP)alpha and peroxisome proliferator-activated receptor (PPAR) gamma, C/EBPalpha, and PPARgamma turns on series of adipocyte genes that give rise to the adipocyte phenotype. Previous findings indicate that C/EBPbeta, a transcriptional activator of the C/EBPalpha and PPARgamma genes, is rapidly expressed after induction, but lacks DNA-binding activity and therefore cannot activate transcription of the C/EBPalpha and PPARgamma genes early in the differentiation program. Acquisition of DNA-binding activity of C/EBPbeta occurs when CHOP-10, a dominant-negative form of C/EBP family members, is down-regulated and becomes hyperphosphorylated as preadipocytes traverse the G1-S checkpoint of mitotic clonal expansion. Evidences are presented in this report that lactacystin, a proteasome inhibitor, up-regulated the CHOP-10 expression, blocked the DNA-binding activity of C/EBPbeta, and subsequently inhibited MCE as well as adipocyte differentiation.
authors.affiliation: Key Laboratory of Molecular Medicine, Ministry of Education, Fudan University Shanghai Medical School, P.O. Box 238, 138 Yi Xue Yuan Road, Shanghai 200032, PR China.
authors.forename: Xi
authors.initials: X
authors.lastname: Li
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Huang
authors.forename: Jie-Gen
authors.initials: JG
authors.lastname: Chen
authors.forename: Lin
authors.initials: L
authors.lastname: Jiang
authors.forename: Hong-Lei
authors.initials: HL
authors.lastname: Liu
authors.forename: De-Guo
authors.initials: DG
authors.lastname: Liu
authors.forename: Tan-Jing
authors.initials: TJ
authors.lastname: Song
authors.forename: Qun
authors.initials: Q
authors.lastname: He
authors.forename: Chun-Gu
authors.initials: CG
authors.lastname: Ma
authors.forename: Duan
authors.initials: D
authors.lastname: Ma
authors.forename: Hou-Yan
authors.initials: HY
authors.lastname: Song
authors.forename: Qi-Qun
authors.initials: QQ
authors.lastname: Tang
mesh_terms: D041721:3T3-L1 Cells; D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D051379:Mice; D008938:Mitosis / Q000187:drug effects; D011485:Protein Binding; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; C497250:Ddit3 protein, mouse; C067713:lactacystin; D051742:Transcription Factor CHOP; D004247:DNA; D051357:Cyclin-Dependent Kinase 2; D000111:Acetylcysteine