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Title: Protein inhibitor of activated STAT3 inhibits adipogenic gene expression

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/EBP{alpha} and PPAR{gamma}, as well as their downstream target genes aP2 and adiponectin. PIAS3 also inhibited C/EBP{alpha} 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.

Authors:
 [1];  [1];  [2];  [3];  [4]
  1. Department of Nutrition, CB 7461, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 (United States)
  2. Department of Medicine, CB 7005, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 (United States)
  3. Department of Pathology and Laboratory Medicine, CB 7525, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 (United States)
  4. Department of Nutrition, CB 7461, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 (United States). E-mail: jharp@unc.edu
Publication Date:
OSTI Identifier:
20798756
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 339; Journal Issue: 3; Other Information: DOI: 10.1016/j.bbrc.2005.10.217; PII: S0006-291X(05)02486-1; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ADIPOSE TISSUE; CYTOPLASM; DEXAMETHASONE; GENES; INSULIN; METABOLIC DISEASES; MICE; PROMOTERS; TRANSCRIPTION; TRANSCRIPTION FACTORS; TRANSDUCERS

Citation Formats

Deng Jianbei, Hua Kunjie, Caveney, Erica J., Takahashi, Nobuyuki, and Harp, Joyce B.. Protein inhibitor of activated STAT3 inhibits adipogenic gene expression. United States: N. p., 2006. Web. doi:10.1016/j.bbrc.2005.10.217.
Deng Jianbei, Hua Kunjie, Caveney, Erica J., Takahashi, Nobuyuki, & Harp, Joyce B.. Protein inhibitor of activated STAT3 inhibits adipogenic gene expression. United States. doi:10.1016/j.bbrc.2005.10.217.
Deng Jianbei, Hua Kunjie, Caveney, Erica J., Takahashi, Nobuyuki, and Harp, Joyce B.. Fri . "Protein inhibitor of activated STAT3 inhibits adipogenic gene expression". United States. doi:10.1016/j.bbrc.2005.10.217.
@article{osti_20798756,
title = {Protein inhibitor of activated STAT3 inhibits adipogenic gene expression},
author = {Deng Jianbei and Hua Kunjie and Caveney, Erica J. and Takahashi, Nobuyuki and Harp, Joyce B.},
abstractNote = {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/EBP{alpha} and PPAR{gamma}, as well as their downstream target genes aP2 and adiponectin. PIAS3 also inhibited C/EBP{alpha} 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.},
doi = {10.1016/j.bbrc.2005.10.217},
journal = {Biochemical and Biophysical Research Communications},
number = 3,
volume = 339,
place = {United States},
year = {Fri Jan 20 00:00:00 EST 2006},
month = {Fri Jan 20 00:00:00 EST 2006}
}