Reversion of lethality and growth defects in Fatiga oxygen-sensor mutant flies by loss of Hypoxia-Inducible Factor-α/Sima

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Hypoxia-Inducible Factor (HIF) prolyl hydroxylase domains (PHDs) have been proposed to act as sensors that have an important role in oxygen homeostasis. In the presence of oxygen, they hydroxylate two specific prolyl residues in HIF-α polypeptides, thereby promoting their proteasomal degradation. So...

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Autores principales:	Centanin, L., Ratcliffe, P.J., Wappner, P.
Formato:	Artículo publishedVersion
Publicado:	2005
Materias:	Drosophila Hypoxia-inducible factor Oxygen sensor Sima Drosophila protein hypoxia inducible factor alpha mutant protein oxygen protein Fatiga unclassified drug article cell size controlled study developmental disorder developmental stage gene mutation genetic code growth disorder lethality mutant nonhuman null allele oxygen sensing priority journal protein depletion protein function regulatory mechanism survival Animals Cell Hypoxia Cell Size DNA-Binding Proteins Drosophila melanogaster Drosophila Proteins Gene Expression Regulation, Developmental Genes, Lethal Hypoxia-Inducible Factor 1, alpha Subunit Larva Oxygen Phenotype Procollagen-Proline Dioxygenase RNA, Messenger Time Factors Metazoa
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_1469221X_v6_n11_p1070_Centanin https://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=artiaex&d=paper_1469221X_v6_n11_p1070_Centanin_oai
Aporte de:	Repositorio Digital de la Universidad de Buenos Aires (UBA) de Universidad de Buenos Aires

id	I28-R145-paper_1469221X_v6_n11_p1070_Centanin_oai
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spelling	I28-R145-paper_1469221X_v6_n11_p1070_Centanin_oai2024-08-16 Centanin, L. Ratcliffe, P.J. Wappner, P. 2005 Hypoxia-Inducible Factor (HIF) prolyl hydroxylase domains (PHDs) have been proposed to act as sensors that have an important role in oxygen homeostasis. In the presence of oxygen, they hydroxylate two specific prolyl residues in HIF-α polypeptides, thereby promoting their proteasomal degradation. So far, however, the developmental consequences of the inactivation of PHDs in higher metazoans have not been reported. Here, we describe novel loss-of-function mutants of fatiga, the gene encoding the Drosophila PHD oxygen sensor, which manifest growth defects and lethality. We also report a null mutation in dHIF-α/sima, which is unable to adapt to hypoxia but is fully viable in normoxic conditions. Strikingly, loss-of-function mutations of sima rescued the developmental defects observed in fatiga mutants and enabled survival to adulthood. These results indicate that the main functions of Fatiga in development, including control of cell size, involve the regulation of dHIF/Sima. © 2005 European Molecular Biology Organization. Fil:Centanin, L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Wappner, P. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. application/pdf http://hdl.handle.net/20.500.12110/paper_1469221X_v6_n11_p1070_Centanin info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar EMBO Rep. 2005;6(11):1070-1075 Drosophila Hypoxia-inducible factor Oxygen sensor Sima Drosophila protein hypoxia inducible factor alpha mutant protein oxygen protein Fatiga unclassified drug article cell size controlled study developmental disorder developmental stage Drosophila gene mutation genetic code growth disorder lethality mutant nonhuman null allele oxygen sensing priority journal protein depletion protein function regulatory mechanism survival Animals Cell Hypoxia Cell Size DNA-Binding Proteins Drosophila melanogaster Drosophila Proteins Gene Expression Regulation, Developmental Genes, Lethal Hypoxia-Inducible Factor 1, alpha Subunit Larva Oxygen Phenotype Procollagen-Proline Dioxygenase RNA, Messenger Time Factors Metazoa Reversion of lethality and growth defects in Fatiga oxygen-sensor mutant flies by loss of Hypoxia-Inducible Factor-α/Sima info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion https://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=artiaex&d=paper_1469221X_v6_n11_p1070_Centanin_oai
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-145
collection	Repositorio Digital de la Universidad de Buenos Aires (UBA)
topic	Drosophila Hypoxia-inducible factor Oxygen sensor Sima Drosophila protein hypoxia inducible factor alpha mutant protein oxygen protein Fatiga unclassified drug article cell size controlled study developmental disorder developmental stage Drosophila gene mutation genetic code growth disorder lethality mutant nonhuman null allele oxygen sensing priority journal protein depletion protein function regulatory mechanism survival Animals Cell Hypoxia Cell Size DNA-Binding Proteins Drosophila melanogaster Drosophila Proteins Gene Expression Regulation, Developmental Genes, Lethal Hypoxia-Inducible Factor 1, alpha Subunit Larva Oxygen Phenotype Procollagen-Proline Dioxygenase RNA, Messenger Time Factors Metazoa
spellingShingle	Drosophila Hypoxia-inducible factor Oxygen sensor Sima Drosophila protein hypoxia inducible factor alpha mutant protein oxygen protein Fatiga unclassified drug article cell size controlled study developmental disorder developmental stage Drosophila gene mutation genetic code growth disorder lethality mutant nonhuman null allele oxygen sensing priority journal protein depletion protein function regulatory mechanism survival Animals Cell Hypoxia Cell Size DNA-Binding Proteins Drosophila melanogaster Drosophila Proteins Gene Expression Regulation, Developmental Genes, Lethal Hypoxia-Inducible Factor 1, alpha Subunit Larva Oxygen Phenotype Procollagen-Proline Dioxygenase RNA, Messenger Time Factors Metazoa Centanin, L. Ratcliffe, P.J. Wappner, P. Reversion of lethality and growth defects in Fatiga oxygen-sensor mutant flies by loss of Hypoxia-Inducible Factor-α/Sima
topic_facet	Drosophila Hypoxia-inducible factor Oxygen sensor Sima Drosophila protein hypoxia inducible factor alpha mutant protein oxygen protein Fatiga unclassified drug article cell size controlled study developmental disorder developmental stage Drosophila gene mutation genetic code growth disorder lethality mutant nonhuman null allele oxygen sensing priority journal protein depletion protein function regulatory mechanism survival Animals Cell Hypoxia Cell Size DNA-Binding Proteins Drosophila melanogaster Drosophila Proteins Gene Expression Regulation, Developmental Genes, Lethal Hypoxia-Inducible Factor 1, alpha Subunit Larva Oxygen Phenotype Procollagen-Proline Dioxygenase RNA, Messenger Time Factors Metazoa
description	Hypoxia-Inducible Factor (HIF) prolyl hydroxylase domains (PHDs) have been proposed to act as sensors that have an important role in oxygen homeostasis. In the presence of oxygen, they hydroxylate two specific prolyl residues in HIF-α polypeptides, thereby promoting their proteasomal degradation. So far, however, the developmental consequences of the inactivation of PHDs in higher metazoans have not been reported. Here, we describe novel loss-of-function mutants of fatiga, the gene encoding the Drosophila PHD oxygen sensor, which manifest growth defects and lethality. We also report a null mutation in dHIF-α/sima, which is unable to adapt to hypoxia but is fully viable in normoxic conditions. Strikingly, loss-of-function mutations of sima rescued the developmental defects observed in fatiga mutants and enabled survival to adulthood. These results indicate that the main functions of Fatiga in development, including control of cell size, involve the regulation of dHIF/Sima. © 2005 European Molecular Biology Organization.
format	Artículo Artículo publishedVersion
author	Centanin, L. Ratcliffe, P.J. Wappner, P.
author_facet	Centanin, L. Ratcliffe, P.J. Wappner, P.
author_sort	Centanin, L.
title	Reversion of lethality and growth defects in Fatiga oxygen-sensor mutant flies by loss of Hypoxia-Inducible Factor-α/Sima
title_short	Reversion of lethality and growth defects in Fatiga oxygen-sensor mutant flies by loss of Hypoxia-Inducible Factor-α/Sima
title_full	Reversion of lethality and growth defects in Fatiga oxygen-sensor mutant flies by loss of Hypoxia-Inducible Factor-α/Sima
title_fullStr	Reversion of lethality and growth defects in Fatiga oxygen-sensor mutant flies by loss of Hypoxia-Inducible Factor-α/Sima
title_full_unstemmed	Reversion of lethality and growth defects in Fatiga oxygen-sensor mutant flies by loss of Hypoxia-Inducible Factor-α/Sima
title_sort	reversion of lethality and growth defects in fatiga oxygen-sensor mutant flies by loss of hypoxia-inducible factor-α/sima
publishDate	2005
url	http://hdl.handle.net/20.500.12110/paper_1469221X_v6_n11_p1070_Centanin https://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=artiaex&d=paper_1469221X_v6_n11_p1070_Centanin_oai
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_version_	1809356756346732544

Reversion of lethality and growth defects in Fatiga oxygen-sensor mutant flies by loss of Hypoxia-Inducible Factor-α/Sima

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