Electronic Resource
Palo Alto, Calif.
:
Annual Reviews
Annual Review of Biochemistry
74 (2005), S. 115-128
ISSN:
0066-4154
Source:
Annual Reviews Electronic Back Volume Collection 1932-2001ff
Topics:
Chemistry and Pharmacology
,
Biology
Notes:
Hypoxia-inducible factor (HIF) is a master transcriptional regulator of hypoxia-inducible genes and consists of a labile ʼ̛ subunit (such as HIF1ʼ̛) and a stable subunit (such as HIF1?‚ or ARNT). In the presence of oxygen, HIFʼ̛ family members are hydroxylated on one of two conserved prolyl residues by members of the egg-laying-defective nine (EGLN) family. Prolyl hydroxylation generates a binding site for a ubiquitin ligase complex containing the von Hippel-Lindau (VHL) tumor suppressor protein, which results in HIFʼ̛ destruction. In addition, the HIFʼ̛ transcriptional activation function is modulated further by asparagine hydroxylation by FIH (factor-inhibiting HIF), which affects recruitment of the coactivators p300 and CBP. These findings provide new mechanistic insights into oxygen sensing by metazoans and are the first examples of protein hydroxylation being used in intracellular signaling. The existence of three human EGLN family members, as well as other putative hydroxylases, raises the possibility that this signal is used in other contexts by other proteins.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1146/annurev.biochem.74.082803.133142
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