Tumour necrosis factor-alpha regulates expression of the CCAAT-enhancer-binding proteins (C/EBPs) alpha and beta and determines the occupation of the C/EBP site in the promoter of the insulin-responsive glucose-transporter gene in 3T3-L1 adipocytes.

Abstract	We have demonstrated previously that treatment of 3T3-L1 adipocytes with tumour necrosis factor-alpha (TNF) results in a rapid (4 h) and significant (75-80%) reduction in the rate of transcription of the GLUT4 gene. Control of GLUT4 gene transcription has been suggested at least in part to reside with the CCAAT-enhancer-binding protein (C/EBP) family (alpha, beta and delta isoforms) of transcription factors. Using electrophoretic mobility shift assays, we have examined the ability of TNF to alter the occupation of the C/EBP site in the GLUT4 promoter. The data suggest that in fully differentiated adipocytes the C/EBP site is a ligand for predominantly alpha/alpha homodimers; however, after exposure to TNF, a shift in occupancy of the site occurs and the ligands become alpha/beta heterodimers and beta/beta homodimers. Partner selection in dimer formation appears to be controlled by selective translocation of the beta-isoform from the cytosol to the nucleus after exposure of the cells to TNF.
Authors	R Jain, S Police, K Phelps, P H Pekala
Journal	The Biochemical journal (Biochem J) Vol. 338 ( Pt 3) Pg. 737-43 (Mar 15 1999) ISSN: 0264-6021 [Print] England
PMID	10051447 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References	CCAAT-Enhancer-Binding Proteins DNA-Binding Proteins Glucose Transporter Type 4 Insulin Monosaccharide Transport Proteins Muscle Proteins Nuclear Proteins Protein Isoforms RNA, Messenger Recombinant Proteins Slc2a4 protein, mouse Tumor Necrosis Factor-alpha DNA
Topics	3T3 Cells Animals Binding Sites CCAAT-Enhancer-Binding Proteins DNA DNA-Binding Proteins (genetics, metabolism) Gene Expression Regulation (drug effects) Glucose Transporter Type 4 Insulin (pharmacology) Mice Monosaccharide Transport Proteins (genetics) Muscle Proteins Nuclear Proteins (genetics, metabolism) Promoter Regions, Genetic Protein Isoforms (genetics, metabolism) RNA, Messenger (genetics, metabolism) Recombinant Proteins (genetics, metabolism) Tumor Necrosis Factor-alpha (pharmacology)

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