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Publication : Protein inhibitor of activated STAT3 inhibits adipogenic gene expression.

First Author  Deng J Year  2006
Journal  Biochem Biophys Res Commun Volume  339
Issue  3 Pages  923-31
PubMed ID  16329991 Mgi Jnum  J:104136
Mgi Id  MGI:3611174 Doi  10.1016/j.bbrc.2005.10.217
Citation  Deng J, et al. (2006) Protein inhibitor of activated STAT3 inhibits adipogenic gene expression. Biochem Biophys Res Commun 339(3):923-31
abstractText  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/EBPalpha and PPARgamma, as well as their downstream target genes aP2 and adiponectin. PIAS3 also inhibited C/EBPalpha 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.
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