Dann Charles E, Bruick Richard K
Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9038, USA.
Biochem Biophys Res Commun. 2005 Dec 9;338(1):639-47. doi: 10.1016/j.bbrc.2005.08.140. Epub 2005 Aug 26.
A ubiquitous pathway by which mammalian cells sense and respond to changes in oxygen availability relies upon the hypoxic induction of a transcription factor, HIF. HIF in turn activates the expression of an assemblage of genes promoting compensatory shifts in the capacity for anaerobic metabolism, O2 delivery, and other adaptive processes. The stability and activity of HIF are each regulated as a function of O2. Both mechanisms are directly mediated by posttranslational modification of this transcription factor: hydroxylation of proline and asparagine residues, respectively. These modifications are performed by members of the Fe(II)- and 2-oxoglutarate-dependent dioxygenase family whose activities are directly and indirectly dependent on cellular O2 levels. As such, these oxygenases fill a role as environmental and metabolic sensors, a paradigm that may extend to other biological pathways.
哺乳动物细胞感知并响应氧可用性变化的一条普遍途径依赖于转录因子HIF的低氧诱导。HIF进而激活一组基因的表达，这些基因促进无氧代谢能力、氧气输送及其他适应性过程的代偿性转变。HIF的稳定性和活性均作为氧的函数受到调控。这两种机制均直接由该转录因子的翻译后修饰介导：分别是脯氨酸和天冬酰胺残基的羟基化。这些修饰由依赖于Fe(II)和2-氧戊二酸的双加氧酶家族成员进行，其活性直接或间接依赖于细胞内氧水平。因此，这些加氧酶充当环境和代谢传感器，这一模式可能扩展到其他生物途径。
