Role of C/EBP homologous protein (CHOP-10) in the programmed activation of CCAAT/enhancer-binding protein-β during adipogenesis

Qi Qun Tang, M. Daniel Lane

Research output: Contribution to journalArticle

Abstract

Hormone induction of growth-arrested preadipocytes triggers mitotic clonal expansion followed by expression of CCAAT/enhancer-binding protein (C/EBP)α and differentiation into adipocytes. The order of these events is critical because C/EBPα is antimitotic and its expression prematurely would block the mitotic clonal expansion required for differentiation. C/EBPβ, a transcriptional activator of the C/EBPα gene, is expressed early in the differentiation program, but lacks DNA-binding activity and fails to localize to centromeres until preadipocytes traverse the G1-S checkpoint of mitotic clonal expansion. Evidence is presented that dominantnegative CHOP-10 expressed by growth-arrested preadipocytes transiently sequesters C/EBPβ by heterodimerization. As preadipocytes reach S phase, CHOP-10 is down-regulated, apparently releasing C/EBPβ from inhibitory constraint and allowing trans-activation of the C/EBPα gene. In support of these findings, up-regulation of CHOP-10 with the protease inhibitor N-acetyl-Leu-Leu-norleucinal prevents activation of C/EBPβ, expression of C/EBPα, and adipogenesis.

Original languageEnglish (US)
Pages (from-to)12446-12450
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number23
DOIs
StatePublished - Nov 7 2000

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Keywords

  • 3T3-L1 preadipocyte
  • Adipocyte
  • Centromere
  • Differentiation
  • Mitotic clonal expansion

ASJC Scopus subject areas

  • Genetics
  • General

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