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

Xi Li, Hai Yan Huang, Jie Gen Chen, Lin Jiang, Hong Lei Liu, De Guo Liu, Tan Jing Song, Qun He, Chun Gu Ma, Duan Ma, Hou Yan Song, Qi Qun Tang

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Hormonal induction triggers a cascade leading to the expression of CCAAT/enhancer-binding protein(C/EBP)α and peroxisome proliferator-activated receptor (PPAR) γ, C/EBPα, and PPARγ turns on series of adipocyte genes that give rise to the adipocyte phenotype. Previous findings indicate that C/EBPβ, a transcriptional activator of the C/EBPα and PPARγ genes, is rapidly expressed after induction, but lacks DNA-binding activity and therefore cannot activate transcription of the C/EBPα and PPARγ genes early in the differentiation program. Acquisition of DNA-binding activity of C/EBPβ 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/EBPβ, and subsequently inhibited MCE as well as adipocyte differentiation.

Original languageEnglish (US)
Pages (from-to)1-6
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume350
Issue number1
DOIs
StatePublished - Nov 10 2006
Externally publishedYes

Keywords

  • C/EBPα
  • C/EBPβ
  • DNA-binding activity
  • Mitotic clonal expansion
  • PPARγ

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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