Signal transduction to hypoxia-inducible factor 1.
Hypoxia-inducible factor 1 (HIF-1) is a transcriptional activator that functions as a master regulator of O2 homeostasis. HIF-1 target genes encode proteins that increase O2 delivery and mediate adaptive responses to O2 deprivation. HIF-1 activity is regulated by the cellular O2 concentration and by the major growth factor-stimulated signal transduction pathways. In human cancer cells, both intratumoral hypoxia and genetic alterations affecting signal transduction pathways lead to increased HIF-1 activity, which promotes angiogenesis, metabolic adaptation, and other critical aspects of tumor progression.
Semenza
Gregg
G
Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, 600 North Wolfe Street, CMSC-1004, Baltimore, MD 21287-3914, USA. gsemenza@jhmi.edu
D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D020935:MAP Kinase Signaling System; D009369:Neoplasms / Q000503:physiopathology / Q000628:therapy; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*
D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D014157:Transcription Factors; C497442:HIF1A protein, human; C576597:ATR protein, human