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Chemical basis for the selectivity of the von Hippel Lindau tumor suppressor pVHL for prolyl-hydroxylated HIF-1alpha.

Abstract:

In animals, the post-translational hydroxylation of hypoxia inducible factor (HIF) is a central mechanism for regulating gene expression in an oxygen-dependent manner. The oxygenase-catalyzed trans-4-prolyl hydroxylation of HIF-alpha increases its affinity for the von Hippel Lindau protein elongin B/C (VCB) ubiquitin ligase complex, leading to HIF-alpha degradation. The level of binding of HIF-alpha to VCB is increased by approximately 1000-fold upon addition of a single oxygen atom to a cons...

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Publication status:
Published

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Publisher copy:
10.1021/bi100358t

Authors


More by this author
Institution:
University of Oxford
Division:
MPLS
Department:
Chemistry
Sub department:
Organic Chemistry
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MPLS
Department:
Chemistry
Sub department:
Organic Chemistry
Role:
Author
Journal:
Biochemistry More from this journal
Volume:
49
Issue:
32
Pages:
6936-6944
Publication date:
2010-08-01
DOI:
EISSN:
1520-4995
ISSN:
0006-2960
Language:
English
Keywords:
Pubs id:
pubs:66117
UUID:
uuid:09524241-9fa9-4435-9e06-208b81829a79
Local pid:
pubs:66117
Source identifiers:
66117
Deposit date:
2012-12-19

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