Tumor necrosis factor α-induced glucose transporter (GLUT-1) mRNA stabilization in 3T3-L1 preadipocytes

Department of Biochemistry, School of Medicine, East Carolina University, Greenville, North Carolina 27858.
Journal of Biological Chemistry (Impact Factor: 4.57). 05/1992; 267(12):8336-41.
Source: PubMed


Tumor necrosis factor alpha (TNF alpha), 12-O-tetradecanoylphorbol-13-acetate and cAMP stimulate hexose transport in quiescent 3T3-L1 preadipocytes by stabilizing the relatively labile mRNA coding for the basal glucose transporter, GLUT-1. The 3'-UTR of GLUT-1 mRNA contains a single copy of the destabilizing AUUUA motif in the context of an AU-rich region. The adenosine-uridine binding factor (AUBF) is a cytosolic protein which interacts with similar AU-rich regions in a variety of labile cytokine and oncogene mRNAs. Here, we demonstrate that AUBF complexes in vitro with GLUT-1 mRNA through the AU-rich portion of the 3'-UTR. AUBF activity is very low in quiescent preadipocytes, but can be up-regulated by agonists such as TPA, TNF alpha, cAMP, and okadaic acid, all of which stabilize GLUT-1 mRNA. The time courses of TNF alpha- and TPA-mediated AUBF up-regulation and GLUT-1 mRNA stabilization are coincident, suggesting a cause and effect relationship.

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    • "For example, the p80 TAF binds to the CAE 2181)2190 to increase GLUT1 mRNA stability and gene expression (Boado 1998; Boado 2000; Tsukamoto et al. 1996). A±U-rich cis-regulatory elements located within the 3¢-UTR of GLUT1 may either stabilize or destabilize the GLUT1 mRNA (Stephens et al. 1992; Levy et al. 1996; McGowan et al. 1997). Hypoxia induces stabilization of both GLUT1 and vascular endothelial growth factor transcripts through interaction of a U-rich region located within nt 1967±2359 of GLUT1 mRNA with cytoplasmic hypoxia-inducible proteins (Levy et al. 1996). "
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    ABSTRACT: The Wnts can be classified into two classes based on their ability to transform cells. The Wnt5a class can antagonize the effects of transforming Wnts partly through effects on cell migration. To understand the mechanisms of regulation of Wnt5a, we investigated its expression in human normal and breast cancer cell lines. Elevation of Wnt5a in HB2, a normal breast epithelial cell line, was linearly correlated with cell density, but this did not occur in cancer cell lines. We examined intracellular events responsible for the regulation of Wnt5a by cell to cell contacts, using various metabolic agents known to affect signal transduction pathways. Agents that selectively blocked protein kinase C (calphostin C) or protein tyrosine kinases (genistein) reduced the level of Wnt5a expression markedly. Protein kinase C activation by phorbol 12-myristate 13-acetate up-regulated Wnt5a partly through prolongation of Wnt5a mRNA half-life. Cytoskeleton reorganization following cytochalasin D treatment caused an induction of Wnt5a, which was associated with changes in cell morphology. Calphostin C did not block these effects, showing that protein kinase C is acting upstream of cytoskeletal modulation. However, the cancer cell lines treated with cytochalasin D showed no changes in cell morphology or Wnt5a induction, suggesting disruption of this regulatory pathway in cancer.
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