Schmid Tobias, Zhou Jie, Brüne Bernhard
University of Kaiserslautern, Faculty of Biology, Department of Cell Biology, Kaiserslautern 67663, Germany.
J Cell Mol Med. 2004 Oct-Dec;8(4):423-31. doi: 10.1111/j.1582-4934.2004.tb00467.x.
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.
氧气感知以及对氧气浓度变化的反应性是细胞生理学的一项基本特性。缺氧（即缺乏O₂）会引发多种适应性反应，这一过程很大程度上受一种名为缺氧诱导因子-1（HIF-1）的转录因子控制。最近的报告表明，除了通过蛋白酶体降解进行传统调控外，其他信号通路也参与了HIF-1α亚基的稳定性调控和/或HIF-1的反式激活。这些调节回路使得HIF-1能够融入细胞存活与细胞死亡的情境中，一般原则是短期轻度缺氧维持细胞活力，而长期严重缺氧则引发细胞死亡。细胞死亡途径与肿瘤抑制因子p53的稳定有关，这种反应在缺氧条件下也能见到。在此，我们总结了近期关于缺氧条件下HIF-1α和p53积累的信息，并提供了一个模型来解释在（病理）生理条件下HIF-1与p53之间的相互作用。
