Activated pp60c-Src leads to elevated hypoxia-inducible factor (HIF)-1alpha expression under normoxia

J Biol Chem. 2002 Nov 8;277(45):42919-25. doi: 10.1074/jbc.M206141200. Epub 2002 Aug 27.

Abstract

Hypoxia-inducible factor (HIF)-1 is a master transcription factor, which up-regulates glycolysis, erythropoiesis, and angiogenesis under hypoxia. HIF-1alpha accumulates in normoxic tumor cells, leading to glycolysis under aerobic conditions. This phenomenon, known as the "Warburg effect," is caused by a yet unknown mechanism. Here we show that transformed cells that express constitutively active pp60(c-Src) (Src) express HIF-1alpha protein under normoxia, which results in the expression of multiple HIF-1alpha target genes. We show that this occurrence is due to an enhanced rate of HIF-1alpha protein synthesis and not due to reduced HIF-1alpha degradation. Furthermore, we show that the Src-induced increase in protein synthesis is due to the global increase in the rate of cap-dependent translation and does not involve inhibition of HIF-1alpha degradation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line
  • DNA Primers
  • Gene Expression Regulation
  • Genes, Reporter
  • Half-Life
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Kinetics
  • Protein Biosynthesis*
  • Proto-Oncogene Proteins pp60(c-src) / metabolism*
  • RNA, Messenger / genetics
  • Recombinant Fusion Proteins / metabolism
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Transfection

Substances

  • DNA Primers
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • RNA, Messenger
  • Recombinant Fusion Proteins
  • Transcription Factors
  • Proto-Oncogene Proteins pp60(c-src)