Sprouty2 Protein Regulates Hypoxia-inducible Factor-α (HIFα) Protein Levels and Transcription of HIFα-responsive Genes.

ABSTRACT: The α-subunits of hypoxia-inducible factors (HIF1α and HIF2α) promote transcription of genes that regulate glycolysis and cell survival and growth. Sprouty2 (Spry2) is a modulator of receptor tyrosine kinase signaling and inhibits cell proliferation by a number of different mechanisms. Because of the seemingly opposite actions of HIFα subunits and Spry2 on cellular processes, we investigated whether Spry2 regulates the levels of HIF1α and HIF2α proteins. In cell lines from different types of tumors in which the decreased protein levels of Spry2 have been associated with poor prognosis, silencing of Spry2 elevated HIF1α protein levels. Increases in HIF1α and HIF2α protein levels due to silencing of Spry2 also up-regulated HIFα target genes. Using HIF1α as a prototype, we show that Spry2 dec

SUBMITTER: Hicks KC 

PROVIDER: S-EPMC4974391 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature