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

Journal Article · · Biochemical and Biophysical Research Communications
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  1. Key Laboratory of Molecular Medicine, Ministry of Education, Fudan University Shanghai Medical School, P.O. Box 238, 138 Yi Xue Yuan Road, Shanghai 200032 (China)
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/EBP{alpha}, and PPAR{gamma} turns on series of adipocyte genes that give rise to the adipocyte phenotype. Previous findings indicate that C/EBP{beta}, a transcriptional activator of the C/EBP{alpha} and PPAR{gamma} genes, is rapidly expressed after induction, but lacks DNA-binding activity and therefore cannot activate transcription of the C/EBP{alpha} and PPAR{gamma} genes early in the differentiation program. Acquisition of DNA-binding activity of C/EBP{beta} occurs when CHOP-10, a dominant-negative form of C/EBP family members, is down-regulated and becomes hyperphosphorylated as preadipocytes traverse the G{sub 1}-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/EBP{beta}, and subsequently inhibited MCE as well as adipocyte differentiation.
OSTI ID:
20854557
Journal Information:
Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1 Vol. 350; ISSN 0006-291X; ISSN BBRCA9
Country of Publication:
United States
Language:
English

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