A common polymorphism in the oxygen-dependent degradation (ODD) domain of hypoxia inducible factor-1alpha (HIF-1alpha) does not impair Pro-564 hydroxylation

Melanie J Percy; Sharon M Mooney; Mary Frances McMullin; Adrian Flores; Terence R J Lappin; Frank S Lee

doi:10.1186/1476-4598-2-31

A common polymorphism in the oxygen-dependent degradation (ODD) domain of hypoxia inducible factor-1alpha (HIF-1alpha) does not impair Pro-564 hydroxylation

Melanie J Percy, Sharon M Mooney, Mary Frances McMullin, Adrian Flores, Terence R J Lappin, Frank S Lee

Research output: Contribution to journal › Article › peer-review

54 Citations (Scopus)

Abstract

The hypoxia-inducible factor (HIF) transcription complex, which is activated by low oxygen tension, controls a diverse range of cellular processes including angiogenesis and erythropoiesis. Under normoxic conditions, the alpha subunit of HIF is rapidly degraded in a manner dependent on hydroxylation of two conserved proline residues at positions 402 and 564 in HIF-1alpha in the oxygen-dependent degradation (ODD) domain. This allows subsequent recognition by the von Hippel-Lindau (VHL) tumor suppressor protein, which targets HIF for degradation by the ubiquitin-proteasome pathway. Under hypoxic conditions, prolyl hydroxylation of HIF is inhibited, allowing it to escape VHL-mediated degradation. The transcriptional regulation of the erythropoietin gene by HIF raises the possibility that HIF may play a role in disorders of erythropoiesis, such as idiopathic erythrocytosis (IE).

Original language	English
Pages (from-to)	31-31
Number of pages	1
Journal	Molecular Cancer Therapeutics
Volume	2
DOIs	https://doi.org/10.1186/1476-4598-2-31
Publication status	Published - 09 Sep 2003

Keywords

Binding Sites
DNA
DNA Mutational Analysis
Female
Humans
Hydroxylation
Hypoxia-Inducible Factor 1, alpha Subunit
Male
Mutation, Missense
Oxygen
Polycythemia
Polymorphism, Genetic
Proline
Transcription Factors

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10.1186/1476-4598-2-31

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@article{33113eab98ae452287b4600cc3f7fc03,

title = "A common polymorphism in the oxygen-dependent degradation (ODD) domain of hypoxia inducible factor-1alpha (HIF-1alpha) does not impair Pro-564 hydroxylation",

abstract = "The hypoxia-inducible factor (HIF) transcription complex, which is activated by low oxygen tension, controls a diverse range of cellular processes including angiogenesis and erythropoiesis. Under normoxic conditions, the alpha subunit of HIF is rapidly degraded in a manner dependent on hydroxylation of two conserved proline residues at positions 402 and 564 in HIF-1alpha in the oxygen-dependent degradation (ODD) domain. This allows subsequent recognition by the von Hippel-Lindau (VHL) tumor suppressor protein, which targets HIF for degradation by the ubiquitin-proteasome pathway. Under hypoxic conditions, prolyl hydroxylation of HIF is inhibited, allowing it to escape VHL-mediated degradation. The transcriptional regulation of the erythropoietin gene by HIF raises the possibility that HIF may play a role in disorders of erythropoiesis, such as idiopathic erythrocytosis (IE).",

keywords = "Binding Sites, DNA, DNA Mutational Analysis, Female, Humans, Hydroxylation, Hypoxia-Inducible Factor 1, alpha Subunit, Male, Mutation, Missense, Oxygen, Polycythemia, Polymorphism, Genetic, Proline, Transcription Factors",

author = "Percy, {Melanie J} and Mooney, {Sharon M} and McMullin, {Mary Frances} and Adrian Flores and Lappin, {Terence R J} and Lee, {Frank S}",

year = "2003",

month = sep,

day = "9",

doi = "10.1186/1476-4598-2-31",

language = "English",

volume = "2",

pages = "31--31",

journal = "Molecular Cancer Therapeutics",

issn = "1535-7163",

publisher = "American Association for Cancer Research Inc.",

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A common polymorphism in the oxygen-dependent degradation (ODD) domain of hypoxia inducible factor-1alpha (HIF-1alpha) does not impair Pro-564 hydroxylation. / Percy, Melanie J; Mooney, Sharon M; McMullin, Mary Frances; Flores, Adrian; Lappin, Terence R J; Lee, Frank S.

In: Molecular Cancer Therapeutics, Vol. 2, 09.09.2003, p. 31-31.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - A common polymorphism in the oxygen-dependent degradation (ODD) domain of hypoxia inducible factor-1alpha (HIF-1alpha) does not impair Pro-564 hydroxylation

AU - Percy, Melanie J

AU - Mooney, Sharon M

AU - McMullin, Mary Frances

AU - Flores, Adrian

AU - Lappin, Terence R J

AU - Lee, Frank S

PY - 2003/9/9

Y1 - 2003/9/9

N2 - The hypoxia-inducible factor (HIF) transcription complex, which is activated by low oxygen tension, controls a diverse range of cellular processes including angiogenesis and erythropoiesis. Under normoxic conditions, the alpha subunit of HIF is rapidly degraded in a manner dependent on hydroxylation of two conserved proline residues at positions 402 and 564 in HIF-1alpha in the oxygen-dependent degradation (ODD) domain. This allows subsequent recognition by the von Hippel-Lindau (VHL) tumor suppressor protein, which targets HIF for degradation by the ubiquitin-proteasome pathway. Under hypoxic conditions, prolyl hydroxylation of HIF is inhibited, allowing it to escape VHL-mediated degradation. The transcriptional regulation of the erythropoietin gene by HIF raises the possibility that HIF may play a role in disorders of erythropoiesis, such as idiopathic erythrocytosis (IE).

AB - The hypoxia-inducible factor (HIF) transcription complex, which is activated by low oxygen tension, controls a diverse range of cellular processes including angiogenesis and erythropoiesis. Under normoxic conditions, the alpha subunit of HIF is rapidly degraded in a manner dependent on hydroxylation of two conserved proline residues at positions 402 and 564 in HIF-1alpha in the oxygen-dependent degradation (ODD) domain. This allows subsequent recognition by the von Hippel-Lindau (VHL) tumor suppressor protein, which targets HIF for degradation by the ubiquitin-proteasome pathway. Under hypoxic conditions, prolyl hydroxylation of HIF is inhibited, allowing it to escape VHL-mediated degradation. The transcriptional regulation of the erythropoietin gene by HIF raises the possibility that HIF may play a role in disorders of erythropoiesis, such as idiopathic erythrocytosis (IE).

KW - Binding Sites

KW - DNA

KW - DNA Mutational Analysis

KW - Female

KW - Humans

KW - Hydroxylation

KW - Hypoxia-Inducible Factor 1, alpha Subunit

KW - Male

KW - Mutation, Missense

KW - Oxygen

KW - Polycythemia

KW - Polymorphism, Genetic

KW - Proline

KW - Transcription Factors

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DO - 10.1186/1476-4598-2-31

M3 - Article

C2 - 14521712

VL - 2

SP - 31

EP - 31

JO - Molecular Cancer Therapeutics

JF - Molecular Cancer Therapeutics

SN - 1535-7163

ER -

A common polymorphism in the oxygen-dependent degradation (ODD) domain of hypoxia inducible factor-1alpha (HIF-1alpha) does not impair Pro-564 hydroxylation

Abstract

Keywords

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