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

Autor: Qi Qun Tang, Hou Yan Song, Chun Gu Ma, Lin Jiang, Hong Lei Liu, Hai Yan Huang, Tanjing Song, De Guo Liu, Qun He, Jie Gen Chen, Xi Li, Duan Ma
Rok vydání: 2006
Předmět:
Zdroj: Biochemical and Biophysical Research Communications. 350:1-6
ISSN: 0006-291X
DOI: 10.1016/j.bbrc.2006.08.188
Popis: 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.
Databáze: OpenAIRE