Maxwell Patrick H
Imperial College, Renal Section, Hammersmith Campus, London, United Kingdom.
Cell Cycle. 2004 Feb;3(2):156-9.
HIF-1 is a transcription factor which acts as a master regulator coordinating oxygen homeostasis. An oxygen sensitive signal controlling HIF-1 is provided by enzymatic hydroxylation reactions which require molecular oxygen and modify specific prolyl and asparaginyl residues in the HIF a subunit. These act as switches-- enabling capture by a specific ubiquitin ligase and preventing transactivator recruitment. An important challenge is to understand how this simple principle is used to tailor the oxygen response system to the diverse settings that occur in complex organisms such as ourselves. The emerging picture is of many parameters which are likely to contribute, including cofactor availability and regulated expression of the hydroxylase enzymes.
缺氧诱导因子-1（HIF-1）是一种转录因子，作为协调氧稳态的主要调节因子发挥作用。一种控制HIF-1的氧敏感信号由酶促羟基化反应提供，该反应需要分子氧并修饰HIF α亚基中的特定脯氨酰和天冬酰胺酰残基。这些残基起到开关的作用——使得能被特定的泛素连接酶捕获，并阻止转录激活因子的募集。一个重要的挑战是要理解这个简单的原理是如何被用于使氧反应系统适应诸如我们自身这样的复杂生物体中出现的各种不同情况的。新出现的情况是，许多参数可能都有作用，包括辅助因子的可用性和羟化酶的调控表达。
