PROLINE HYDROXYLATION AND GENE EXPRESSION
Top Cited Papers
- 1 June 2005
- journal article
- review article
- Published by Annual Reviews in Annual Review of Biochemistry
- Vol. 74 (1) , 115-128
- https://doi.org/10.1146/annurev.biochem.74.082803.133142
Abstract
▪ Abstract Hypoxia-inducible factor (HIF) is a master transcriptional regulator of hypoxia-inducible genes and consists of a labile α subunit (such as HIF1α) and a stable β subunit (such as HIF1β or ARNT). In the presence of oxygen, HIFα 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 HIFα destruction. In addition, the HIFα 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.Keywords
This publication has 112 references indexed in Scilit:
- Activation of HIF-1α mRNA by hypoxia and iron chelator in isolated rat carotid bodyNeuroscience Letters, 2004
- Drosophila Cyclin D/Cdk4 Requires Hif-1 Prolyl Hydroxylase to Drive Cell GrowthDevelopmental Cell, 2004
- The von Hippel Lindau/Hypoxia-inducible Factor (HIF) Pathway Regulates the Transcription of the HIF-Proline Hydroxylase Genes in Response to Low OxygenJournal of Biological Chemistry, 2003
- Hypoxic induction of hypoxia-inducible factor-1α and oxygen-regulated gene expression in mitochondrial DNA-depleted HeLa cellsBiochemical and Biophysical Research Communications, 2002
- HIF-1α-prolyl hydroxylase: molecular target of nitric oxide in the hypoxic signal transduction pathwayBiochemical and Biophysical Research Communications, 2002
- Structural basis for the recognition of hydroxyproline in HIF-1α by pVHLNature, 2002
- Independent function of two destruction domains in hypoxia-inducible factor-α chains activated by prolyl hydroxylationThe EMBO Journal, 2001
- SM-20 Is a Novel Mitochondrial Protein That Causes Caspase-dependent Cell Death in Nerve Growth Factor-dependent NeuronsPublished by Elsevier ,2001
- Mechanism of regulation of the hypoxia-inducible factor-1alpha by the von Hippel-Lindau tumor suppressor proteinThe EMBO Journal, 2000
- Identification of Alternative Spliced Variants of Human Hypoxia-inducible Factor-1αPublished by Elsevier ,2000