Tumor necrosis factor alpha-induced glucose transporter (GLUT-1) mRNA stabilization in 3T3-L1 preadipocytes. Regulation by the adenosine-uridine binding factor.
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.
Stephens
J M
JM
Department of Biochemistry, School of Medicine, East Carolina University, Greenville, North Carolina 27858.
Carter
B Z
BZ
Pekala
P H
PH
Malter
J S
JS
D016475:3T3 Cells; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000494:pharmacology; D004247:DNA / Q000235:genetics; D004988:Ethers, Cyclic / Q000494:pharmacology; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000235:genetics*; D019319:Okadaic Acid; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D015854:Up-Regulation
D004988:Ethers, Cyclic; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019319:Okadaic Acid; D015124:8-Bromo Cyclic Adenosine Monophosphate; D004247:DNA; D000242:Cyclic AMP; D013755:Tetradecanoylphorbol Acetate