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.