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HIF-1: master and commander of the hypoxic world. A pharmacological approach to its regulation by siRNAs.

Abstract：

:The hypoxia-inducible factor-1 (HIF-1) is primarily involved in the sensing and adapting of cells to changes in the O2 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 O2 concentrations. HIF-1 regulation by post-translational modification is the central theme of the scenario of O2 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 O2 concentrations.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Mazure NM,Brahimi-Horn MC,Berta MA,Benizri E,Bilton RL,Dayan F,Ginouvès A,Berra E,Pouysségur J

doi

10.1016/j.bcp.2004.04.022

subject

Has Abstract

pub_date

2004-09-15 00:00:00

pages

971-80

issue

6

eissn

0006-2952

issn

1873-2968

pii

S0006295204003508

journal_volume

68

pub_type

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