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Publication : Lactacystin inhibits 3T3-L1 adipocyte differentiation through induction of CHOP-10 expression.

First Author  Li X Year  2006
Journal  Biochem Biophys Res Commun Volume  350
Issue  1 Pages  1-6
PubMed ID  16996026 Mgi Jnum  J:114523
Mgi Id  MGI:3689266 Doi  10.1016/j.bbrc.2006.08.188
Citation  Li X, et al. (2006) Lactacystin inhibits 3T3-L1 adipocyte differentiation through induction of CHOP-10 expression. Biochem Biophys Res Commun 350(1):1-6
abstractText  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.
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