J. Lipid Res. Please sign the JLR Guestbook
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1194/jlr.M700545-JLR200 on January 10, 2008

Papers In Press, published online ahead of print April 1, 2008
J. Lipid Res., doi:10.1194/jlr.M700545-JLR200
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Data
Right arrow All Versions of this Article:
M700545-JLR200v1
49/4/880    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Google Scholar
Right arrow Articles by Takahashi, Y.
Right arrow Articles by Sato, R.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Takahashi, Y.
Right arrow Articles by Sato, R.
Journal of Lipid Research, Vol. 49, 880-892, April 2008
Copyright © 2008 by American Society for Biochemistry and Molecular Biology

TRB3 suppresses adipocyte differentiation by negatively regulating PPAR{gamma} transcriptional activityboxs

Yu Takahashi1,*, Nobumichi Ohoka1,*,{dagger}, Hidetoshi Hayashi2,§ and Ryuichiro Sato2,*,{dagger}

* Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo 113-8657, Japan
{dagger} Basic Research Activities for Innovative Biosciences, Tokyo 105-0001, Japan
§ Department of Molecular Health Sciences, Graduate School of Pharmaceutical Sciences, Nagoya City University, Mizuho, Nagoya 467-8603, Japan

boxs The online version of this article (available at http://www.jlr.org) contains supplementary data in the form of four figures.

Published, JLR Papers in Press, January 10, 2008.

1 Y. Takahashi and N. Ohoka contributed equally to this work.

2 To whom correspondence should be addressed. e-mail: hhayashi{at}phar.nagoya-cu.ac.jp (H.H.);aroysato{at}mail.ecc.u-tokyo.ac.jp (R.S.)

In the course of an effort to identify the regulators for peroxisome proliferator-activated receptor {gamma} (PPAR{gamma})-dependent perilipin gene expression, we found that tribbles homolog 3 (TRB3), containing a single kinase domain without enzymatic activity, downregulates PPAR{gamma} transcriptional activities by protein-protein interaction. We examined the role that TRB3 plays in adipocyte differentiation in 3T3-L1 cells. TRB3 gene and protein expression was increased during adipocyte differentiation concomitantly with an increase in the mRNA levels of CCAAT/enhancer binding protein homologous protein. The physical interaction between TRB3 and PPAR{gamma} was also verified in 3T3-L1 adipocytes. Forced TRB3 expression in 3T3-L1 cells decreased the mRNA levels of PPAR{gamma}-target genes and intracellular triglyceride levels, whereas knockdown of TRB3 expression by RNA interference increased them. TRB3 also inhibits PPAR{gamma}-dependent adipocyte differentiation in lentivirus-mediated PPAR{gamma}-expressing 3T3-L1 cells. These results provide evidence that TRB3 acts as a potent negative regulator of PPAR{gamma}, a master regulator of adipocyte differentiation, and tightly controls adipogenesis.

Supplementary key words tribbles homolog 3 • perilipin • triglyceride • 3T3-L1 • peroxisome proliferator-activated receptor {gamma}

Abbreviations: AF, activation function; C/EBP, CCAAT/enhancer binding protein; CHOP, C/EBP homologous protein; ER, endoplasmic reticulum; GFP, green fluorescent protein; PPAR, peroxisome proliferator-activated receptor; PPRE, PPAR-response element; RXR, retinoid X receptor; shRNA, short hairpin RNA; SREBP, sterol-regulatory element binding protein; TRB3, tribbles homolog 3






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Journal of Biological Chemistry 
 Molecular and Cellular Proteomics   ASBMB Today 
Copyright © 2008 by the American Society for Biochemistry and Molecular Biology.