Transcriptional and Translational Downregulation of Thioredoxin Interacting Protein Is Required for Metabolic Reprogramming during G(1).

ABSTRACT: Growth factor signaling drives increased glucose uptake and glycolysis-the Warburg effect-that supports macromolecular synthesis necessary for cell growth and proliferation. Thioredoxin interacting protein (TXNIP), a direct and glucose-induced transcriptional target of MondoA, is a potent negative regulator of glucose uptake and utilization. Thus, TXNIP may inhibit cell growth by restricting substrate availability for macromolecular synthesis. To determine TXNIP's contribution to metabolic reprogramming, we examined MondoA and TXNIP as cells exit quiescence and enter G(1). Serum stimulation of quiescent immortal diploid fibroblasts resulted in an acute upregulation of glucose uptake and glycolysis coinciding with downregulation of TXNIP expression. Ectopic expression of either MondoA or TX

SUBMITTER: Elgort MG 

PROVIDER: S-EPMC3092257 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature