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Mechanisms linking the ubiquitin proteasome system to adipocyte gene expression
Author(s) -
Batiz Linda K.,
Auld Corinth A.,
Fernandes Karishma M.,
Morrison Ron F.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a164-a
Subject(s) - adipocyte , proteasome , ubiquitin , gene , gene expression , microbiology and biotechnology , biology , genetics , endocrinology , adipose tissue
Knowledge concerning adipocyte gene expression is central to understanding molecular mechanisms regulating hyperplastic obesity. Degradation of regulatory proteins by the Ubiquitin Proteasome System (UPS) known to play an important role in numerous cell processes, including cell cycle progression, signal transduction, and transcriptional regulation. Using the 3T3‐L1 preadipocyte cell line as a model, we investigated the role of the UPS on adipocyte gene expression. We observed that treating fully differentiated adipocytes with epoxomicin (epox), a potent, specific inhibitor of the 26S proteasome, resulted in dramatic suppression of mRNA accumulation for various adipocyte genes including adipsin, aP2, leptin, and adiponectin, with no apparent affect on cell morphology. This effect on mRNA accumulation was time‐dependent with marked suppression within 6 hrs of treatment and complete suppression 18 hrs following UPS blockade. Suppression of mRNA accumulation was dose‐dependent for epoxomicin as well as specific to inhibition of the 26S proteasome as mRNA suppression was obtained with a structurally different, proteasome specific inhibitor, lactacystin. Epox‐mediated mRNA suppression was not affected by concomitant treatment with potent synthetic ligands for PPARgamma. Furthermore, UPS blockade had no affect on PPARgamma or C/EBPalpha protein accumulation. Concomitant treatment of Epox with cycloheximide prevented the observed effect of UPS blockade on adipocyte gene expression, suggesting an indirect mechanism involving protein synthesis. Work supported by grants from American Heart Association (0265418U) and NIH (1R21DK072067‐01).