HIF-1 and p53: communication of transcription factors under hypoxia.
Oxygen sensing and reactivity to changes in the concentration of oxygen is a fundamental property of cell physiology. The lack of O(2) (hypoxia) is transmitted into many adaptive responses, a process that is largely controlled by a transcription factor known as hypoxia inducible factor-1 (HIF-1). More recent reports suggest that besides its traditional regulation via proteasomal degradation other signaling pathways contribute to stability regulation of the HIF-1alpha subunit and/or HIF-1 transactivation. These regulatory circuits allow for the integration of HIF-1 into scenarios of cell-survival vs. cell-death with the rule of the thumb that short-term mild hypoxia maintains cell viability while prolonged and severe hypoxia provokes cell demise. Cell death pathways are associated with stabilization of the tumor suppressor p53, a response also seen under hypoxic conditions. Here we summarize recent information on accumulation of HIF-1alpha and p53 under hypoxia and provide a model to explain the communication between HIF-1 and p53 under (patho)physiological conditions.
Schmid
Tobias
T
University of Kaiserslautern, Faculty of Biology, Department of Cell Biology, Kaiserslautern 67663, Germany.
Zhou
Jie
J
Brüne
Bernhard
B
D000818:Animals; D017209:Apoptosis; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D000860:Hypoxia; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008954:Models, Biological; D008957:Models, Genetic; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000737:chemistry / Q000502:physiology*; D010100:Oxygen / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000502:physiology*; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000502:physiology*
D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D046988:Proteasome Endopeptidase Complex; D010100:Oxygen