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Retinoic acid blocks adipogenesis by inhibiting C/EBPbeta-mediated transcription
Journal article   Open access   Peer reviewed

Retinoic acid blocks adipogenesis by inhibiting C/EBPbeta-mediated transcription

E J Schwarz, M J Reginato, D Shao, S L Krakow and M A Lazar
Molecular and cellular biology, v 17(3), pp 1552-1561
Mar 1997
PMID: 9032283
url
https://doi.org/10.1128/mcb.17.3.1552View
Published, Version of Record (VoR)Open Access (License Unspecified) Open

Abstract

3T3 Cells Adipocytes - cytology Adipocytes - drug effects Animals CCAAT-Enhancer-Binding Proteins Cell Differentiation DNA-Binding Proteins - genetics DNA-Binding Proteins - physiology Gene Expression Regulation - drug effects Gene Expression Regulation - physiology Ligands Mice Nuclear Proteins - genetics Nuclear Proteins - physiology Receptors, Cytoplasmic and Nuclear - genetics Receptors, Retinoic Acid - physiology Recombinant Fusion Proteins Transcription Factors - genetics Transcription, Genetic - drug effects Transcription, Genetic - physiology Transcriptional Activation Transfection Tretinoin - pharmacology
Adipocyte differentiation is thought to involve sequential induction of the transcription factors C/EBPbeta, peroxisome proliferator-activated receptor gamma (PPARgamma), and C/EBPalpha. C/EBPalpha expression is both necessary and sufficient for adipocyte differentiation. Here we report that ectopic expression of either C/EBPalpha or C/EBPbeta induces PPARgamma expression and adipogenesis and that retinoic acid (RA) completely inhibits adipogenesis by either form of C/EBP. In studies of normal preadipocytes, RA does not prevent C/EBPbeta induction but blocks induction of PPARgamma, C/EBPalpha, and adipogenesis. In transient transfection studies, liganded RA receptor (RAR) specifically blocks transcriptional activation by either C/EBPalpha or C/EBPbeta. These results strongly suggest that C/EBPalpha substitutes for C/EBPbeta to induce adipocyte differentiation and that liganded RAR inhibits adipogenesis by blocking C/EBPbeta-mediated induction of downstream genes.

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Web of Science research areas
Biochemistry & Molecular Biology
Cell Biology
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