Reversible Inactivation of HIF-1 Prolyl Hydroxylases Allows Cell Metabolism to Control Basal HIF-1*
نویسندگان
چکیده
منابع مشابه
Hypoxia-inducible factor-1 (HIF-1) promotes its degradation by induction of HIF-alpha-prolyl-4-hydroxylases.
An important regulator involved in oxygen-dependent gene expression is the transcription factor HIF (hypoxia-inducible factor), which is composed of an oxygen-sensitive alpha-subunit (HIF-1alpha or HIF-2alpha) and a constitutively expressed beta-subunit. In normoxia, HIF-1alpha is destabilized by post-translational hydroxylation of Pro-564 and Pro-402 by a family of oxygen-sensitive dioxygenase...
متن کاملA conserved family of prolyl-4-hydroxylases that modify HIF.
Mammalian cells respond to changes in oxygen availability through a conserved pathway that is regulated by the hypoxia-inducible factor (HIF). The alpha subunit of HIF is targeted for degradation under normoxic conditions by a ubiquitin-ligase complex that recognizes a hydroxylated proline residue in HIF. We identified a conserved family of HIF prolyl hydoxylase (HPH) enzymes that appear to be ...
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Tumour hypoxia is a well-known microenvironmental factor that causes cancer progression and resistance to cancer treatment. This involves multiple mechanisms of which the best-understood ones are mediated through transcriptional gene activation by the hypoxia-inducible factors (HIFs). HIFs in turn are regulated in response to oxygen availability by a family of iron- and 2-oxoglutarate-dependent...
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The AMP-activated protein kinase is found in all eukaryotic cells. Once activated, the kinase switches on ATP-producing catabolic pathways and switches off ATP-consuming processes,both via direct phosphorylation of downstream targets, and thus is called a cellular energy regulator . A variety of novel downstream target proteins have been discovered recently, which provide new insight into eluci...
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Hypoxia is a hallmark of solid cancers and triggers the transcription of genes responsible for cell survival. The transcription factor Hypoxia-Inducible Factor 1 (HIF-1) is a key regulator in this response and frequently activated in human cancer. HIF-1 activation is associated with tumor aggressiveness and poor clinical outcome and, therefore, may provide an attractive therapeutic target. Here...
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ژورنال
عنوان ژورنال: Journal of Biological Chemistry
سال: 2005
ISSN: 0021-9258
DOI: 10.1074/jbc.m508718200