Adipocytic conversion of 3T3-L1 cells is dependent on induction of transcription factors from the C/EBP family that activate promoters of adipogenic genes. We find that expression of CHOP, a nuclear protein that dimerizes avidly with C/EBP isoforms α and β and directs the resulting heterodimer away from classic C/EBP-binding sites, markedly inhibits this differentiation process. Surprisingly, the presence of CHOP early in the differentiation process inhibits C/EBPα and β gene expression. Ectopic expression of C/EBPα bypasses the inhibitory effect of CHOP on differentiation, providing further evidence that CHOP action is mediated by inhibition of C/EBPα gene expression rather than merely inhibiting the encoded protein's DNA-binding activity. A similar pattern of attenuated expression of C/EBPα and β is also observed in cells induced to differentiate in media with low glucose concentration. This stressed culture condition is associated with induction of endogenous CHOP and marked attenuation of the differentiation process. Our data suggest that CHOP functions as an inducible inhibitor of adipocytic differentiation in response to metabolic stress. It does so by interfering with the accumulation of adipogenic C/EBP isoforms.
|Original language||English (US)|
|Number of pages||8|
|State||Published - 1995|
ASJC Scopus subject areas
- Molecular Biology
- Biochemistry, Genetics and Molecular Biology(all)
- Immunology and Microbiology(all)