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. 1999 Mar 15;338(Pt 3):737–743.

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.

R Jain 1, S Police 1, K Phelps 1, P H Pekala 1
PMCID: PMC1220111  PMID: 10051447

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.

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Selected References

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