HIF-1:: master and commander of the hypoxic world -: A pharmacological approach to its regulation by siRNAs
HIF-1:: master and commander of the hypoxic world -: A pharmacological approach to its regulation by siRNAs
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DOI：
10.1016/j.bcp.2004.04.022
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发表时间：
2004-09-15
影响因子：
5.8
通讯作者：
Pouysségur, J
中科院分区：
文献类型：
--
作者：
Mazure, NM;Brahimi-Horn, MC;Pouysségur, J
缺氧诱导因子-1（HIF-1）主要参与细胞对氧水平变化的感知和适应，这对细胞的生存至关重要。重要的是，这个关键的转录因子被严格调控，以使细胞响应范围广泛的O（2）浓度。通过翻译后修饰调节HIF-1是O（2）稳态的中心主题。HIF-1的α亚基是主要的参与者，而辅助参与者（PHDs，FIH-1，ARD 1，CITED 2，p300.）所有这些都增加了大结局的复杂性。HIF-1的表达和活化与肿瘤进展和对癌症治疗的抗性相关。我们将介绍参与HIF-1调节的不同参与者，以及它们通过siRNA失效的作用机制，并讨论靶向HIF-1的治疗方法，以选择性地杀死适应低O（2）浓度的肿瘤细胞。(C)2004年爱思唯尔公司All rights reserved.
The hypoxia-inducible factor-1 (HIF-1) is primarily involved in the sensing and adapting of cells to changes in the O(2) level, which is essential for their viability. It is important that this critical transcription factor be tightly regulated in order for cells to respond to a wide range of O(2) concentrations. HIF-1 regulation by post-translational modification is the central theme of the scenario of O(2) homeostasis. The alpha subunit of HIF-1 is the principal actor while the supporting actors (PHDs, FIH-1, ARD1, CITED2, p300...) all contribute to the complexity of the grand finale. It is well established that HIF-1 expression and activation correlates with tumor progression and resistance to cancer treatments. We will introduce the different actors involved in HIF-1 regulation, and their mechanisms of action via invalidation by siRNAs and discuss therapies targeting HIF-1, to selectively kill tumor cells that adapt to low O(2) concentrations. (C) 2004 Elsevier Inc. All rights reserved.