Protein inhibitor of activated STAT3 inhibits adipogenic gene expression

Jianbei Deng, Kunjie Hua, Erica J. Caveney, Nobuyuki Takahashi, Joyce B. Harp

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

Abstract

Protein inhibitor of activated STAT3 (PIAS3), a cytokine-induced repressor of signal transducer and activator of transcription 3 (STAT3) and a modulator of a broad array of nuclear proteins, is expressed in white adipose tissue, but its role in adipogenesis is not known. Here, we determined that PIAS3 was constitutively expressed in 3T3-L1 cells at all stages of adipogenesis. However, it translocated from the nucleus to the cytoplasm 4 days after induction of differentiation by isobutylmethylxanthine, dexamethasone, and insulin (MDI). In ob/ob mice, PIAS3 expression was increased in white adipose tissue depots compared to lean mice and was found in the cytoplasm of adipocytes. Overexpression of PIAS3 in differentiating preadipocytes, which localized primarily to the nucleus, inhibited mRNA level gene expression of adipogenic transcription factors C/EBPα and PPARγ, as well as their downstream target genes aP2 and adiponectin. PIAS3 also inhibited C/EBPα promoter activation mediated specifically by insulin, but not dexamethasone or isobutylmethylxanthine. Taken together, these data suggest that PIAS3 may play an inhibitory role in adipogenesis by modulating insulin-activated transcriptional activation events. Increased PIAS3 expression in adipose tissue may play a role in the metabolic disturbances of obesity.

Original languageEnglish
Pages (from-to)923-931
Number of pages9
JournalBiochemical and biophysical research communications
Volume339
Issue number3
DOIs
Publication statusPublished - 2006 Jan 20
Externally publishedYes

Keywords

  • Adipogenesis
  • C/EBPα
  • Insulin
  • PIAS3
  • PPARγ

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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