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• W1523909433 startingPage "13580" @default.
• W1523909433 abstract "We have previously demonstrated the ability of tumor necrosis factor-alpha (TNF) to down-regulate the expression of GLUT4 (insulin-responsive glucose transporter) and C/EBP-alpha (CCAAT/enhancer-binding protein) (Stephens J. M., and Pekala, P. H. (1991) J. Biol. Chem. 266, 21839-21845). As C/EBP-alpha has been suggested to control GLUT4 expression, we have examined the time course for attenuation of transcription of these genes. Run-on transcription assays indicate a coordinate transcriptional repression of both GLUT4 and C/EBP-alpha genes (as well as the 422/aP2 gene, the adipocyte lipid-binding protein, whose expression has also been proposed to be controlled by C/EBP-alpha). Inhibition of transcription was observed within 1 h of TNF addition, with maximal suppression observed after 4 h. The inhibition was not blocked by cycloheximide. Okadaic acid treatment (1 h, 0.5 microM) also resulted in the coordinate transcriptional repression of the C/EBP-alpha, GLUT4, and 422/aP2 genes, consistent with involvement of a kinase-phosphatase system in the regulation of these genes. The decrease in C/EBP-alpha protein content was detectable 4 h after TNF addition and declined to 25% of controls within 24 h. A minor decrease in the protein content of GLUT4 was observed during the first 24 h of exposure to TNF; however, after 72 h of exposure GLUT4 protein was not detectable. The rapid coordinate transcriptional regulation of C/EBP-alpha, GLUT4, and 422/aP2 by TNF in the presence of cycloheximide suggests that the TNF-induced loss of GLUT4 protein may be mediated by a post-translational modification of an existing transcription factor. However, the rapid loss of C/EBP-alpha protein may be a contributing factor to further transcriptional suppression of the GLUT4 gene at the later time points. In addition to the transcriptional effect, we report that TNF-induced destabilization of these mRNAs contributes to decreased expression of all three genes." @default.
• W1523909433 created "2016-06-24" @default.
• W1523909433 creator A5012135517 @default.
• W1523909433 creator A5018754969 @default.
• W1523909433 date "1992-07-01" @default.
• W1523909433 modified "2023-10-02" @default.
• W1523909433 title "Transcriptional repression of the C/EBP-alpha and GLUT4 genes in 3T3-L1 adipocytes by tumor necrosis factor-alpha. Regulations is coordinate and independent of protein synthesis." @default.
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• W1523909433 doi "https://doi.org/10.1016/s0021-9258(18)42251-x" @default.
• W1523909433 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/1618860" @default.
• W1523909433 hasPublicationYear "1992" @default.
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