Lactacystin inhibits 3T3-L1 adipocyte differentiation through induction of CHOP-10 expression.
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.
Li
Xi
X
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.
Huang
Hai-Yan
HY
Chen
Jie-Gen
JG
Jiang
Lin
L
Liu
Hong-Lei
HL
Liu
De-Guo
DG
Song
Tan-Jing
TJ
He
Qun
Q
Ma
Chun-Gu
CG
Ma
Duan
D
Song
Hou-Yan
HY
Tang
Qi-Qun
QQ
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
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