spacer gif spacer gif spacer gif spacer gif spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents    

doi: 10.1242/10.1242/jcs.00655

This Article
Right arrow Summary Freely available
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Related articles in JCS
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Masson, N.
Right arrow Articles by Ratcliffe, P. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Masson, N.
Right arrow Articles by Ratcliffe, P. J.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

HIF prolyl and asparaginyl hydroxylases in the biological response to intracellular O2 levels

Norma Masson and Peter J. Ratcliffe*

The Henry Wellcome Building of Genomic Medicine, Roosevelt Drive, Oxford OX3 7BN, UK



View larger version (22K):

[in a new window]
  		Fig. 1. Two independent hydroxylation pathways regulate HIF activity in response to cellular oxygen level. In normoxia, oxygen availability enables PHD-dependent prolyl hydroxylation of the HIF-{alpha} ODD. This prolyl hydroxylation allows binding of the VHL E3 ligase leading to ubiquitylation and degradation of HIF-{alpha} subunits. Oxygen availability also enables FIH-dependent asparaginyl hydroxylation of the C-TAD, blocking interaction with the p300/CBP co-activator. In hypoxia, the PHD and FIH enzymes are inactive and the lack of hydroxylation results in stable HIF-{alpha} able to form a DNA-binding heterodimer with HIF-ß and recruit p300/CBP at the C-TAD.

 


View larger version (22K):

[in a new window]
  		Fig. 2. HIF-dependent responses to O2 may be modulated by the cellular environment. Multiple points of interaction exist between the cellular environment and HIF hydroxylase pathways that have the potential to provide precisely tuned physiological responses to hypoxia.

 


View larger version (15K):

[in a new window]
  		Fig. 3. Proposed order of binding of co-substrates and prime substrate by the HIF hydroxylases. Following binding of dioxygen, one oxygen atom is incorporated into the hydroxylated HIF residue and the other oxidises 2-oxoglutarate forming succinate and CO2.

 

Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?



© The Company of Biologists Ltd 2003