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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    • "Taken together, these results suggest the possibility that one mechanism of regulation may involve the prolongation of mRNA half-life at the transcription level by stimulating AP-1-mediated transactivation of Wnt5a in confluent cells through inactivation of GSK3 kinase by PKC. In addition to this, the Wnt5a mRNA contains several AUUUA sequences in its 3' untranslated region, suggesting that phosphorylation by PKC could also play a role in the regulation of the activity of AU-binding proteins (Gillis and Malter, 1991; Stephens et al, 1991), leading to stabilization of Wnt5a mRNA. Stabilization of actin cables can block cell movement and, at confluence, changes occur in the actin cables, resulting in changes in cell morphology. "
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