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PHD1 Links Cell-Cycle Progression to Oxygen Sensing through Hydroxylation of the Centrosomal Protein Cep192

PHD1 belongs to the family of prolyl-4-hydroxylases (PHDs) that is responsible for posttranslational modification of prolines on specific target proteins. Because PHD activity is sensitive to oxygen levels and certain byproducts of the tricarboxylic acid cycle, PHDs act as sensors of the cell’s meta...

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Autores principales: Moser, Sandra C., Bensaddek, Dalila, Ortmann, Brian, Maure, Jean-Francois, Mudie, Sharon, Blow, J. Julian, Lamond, Angus I., Swedlow, Jason R., Rocha, Sonia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3757158/
https://www.ncbi.nlm.nih.gov/pubmed/23932902
http://dx.doi.org/10.1016/j.devcel.2013.06.014
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author Moser, Sandra C.
Bensaddek, Dalila
Ortmann, Brian
Maure, Jean-Francois
Mudie, Sharon
Blow, J. Julian
Lamond, Angus I.
Swedlow, Jason R.
Rocha, Sonia
author_facet Moser, Sandra C.
Bensaddek, Dalila
Ortmann, Brian
Maure, Jean-Francois
Mudie, Sharon
Blow, J. Julian
Lamond, Angus I.
Swedlow, Jason R.
Rocha, Sonia
author_sort Moser, Sandra C.
collection PubMed
description PHD1 belongs to the family of prolyl-4-hydroxylases (PHDs) that is responsible for posttranslational modification of prolines on specific target proteins. Because PHD activity is sensitive to oxygen levels and certain byproducts of the tricarboxylic acid cycle, PHDs act as sensors of the cell’s metabolic state. Here, we identify PHD1 as a critical molecular link between oxygen sensing and cell-cycle control. We show that PHD1 function is required for centrosome duplication and maturation through modification of the critical centrosome component Cep192. Importantly, PHD1 is also required for primary cilia formation. Cep192 is hydroxylated by PHD1 on proline residue 1717. This hydroxylation is required for binding of the E3 ubiquitin ligase SCF(Skp2), which ubiquitinates Cep192, targeting it for proteasomal degradation. By modulating Cep192 levels, PHD1 thereby affects the processes of centriole duplication and centrosome maturation and contributes to the regulation of cell-cycle progression.
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spelling pubmed-37571582013-08-30 PHD1 Links Cell-Cycle Progression to Oxygen Sensing through Hydroxylation of the Centrosomal Protein Cep192 Moser, Sandra C. Bensaddek, Dalila Ortmann, Brian Maure, Jean-Francois Mudie, Sharon Blow, J. Julian Lamond, Angus I. Swedlow, Jason R. Rocha, Sonia Dev Cell Article PHD1 belongs to the family of prolyl-4-hydroxylases (PHDs) that is responsible for posttranslational modification of prolines on specific target proteins. Because PHD activity is sensitive to oxygen levels and certain byproducts of the tricarboxylic acid cycle, PHDs act as sensors of the cell’s metabolic state. Here, we identify PHD1 as a critical molecular link between oxygen sensing and cell-cycle control. We show that PHD1 function is required for centrosome duplication and maturation through modification of the critical centrosome component Cep192. Importantly, PHD1 is also required for primary cilia formation. Cep192 is hydroxylated by PHD1 on proline residue 1717. This hydroxylation is required for binding of the E3 ubiquitin ligase SCF(Skp2), which ubiquitinates Cep192, targeting it for proteasomal degradation. By modulating Cep192 levels, PHD1 thereby affects the processes of centriole duplication and centrosome maturation and contributes to the regulation of cell-cycle progression. Cell Press 2013-08-26 /pmc/articles/PMC3757158/ /pubmed/23932902 http://dx.doi.org/10.1016/j.devcel.2013.06.014 Text en © 2013 The Authors https://creativecommons.org/licenses/by/3.0/ Open Access under CC BY 3.0 (https://creativecommons.org/licenses/by/3.0/) license
spellingShingle Article
Moser, Sandra C.
Bensaddek, Dalila
Ortmann, Brian
Maure, Jean-Francois
Mudie, Sharon
Blow, J. Julian
Lamond, Angus I.
Swedlow, Jason R.
Rocha, Sonia
PHD1 Links Cell-Cycle Progression to Oxygen Sensing through Hydroxylation of the Centrosomal Protein Cep192
title PHD1 Links Cell-Cycle Progression to Oxygen Sensing through Hydroxylation of the Centrosomal Protein Cep192
title_full PHD1 Links Cell-Cycle Progression to Oxygen Sensing through Hydroxylation of the Centrosomal Protein Cep192
title_fullStr PHD1 Links Cell-Cycle Progression to Oxygen Sensing through Hydroxylation of the Centrosomal Protein Cep192
title_full_unstemmed PHD1 Links Cell-Cycle Progression to Oxygen Sensing through Hydroxylation of the Centrosomal Protein Cep192
title_short PHD1 Links Cell-Cycle Progression to Oxygen Sensing through Hydroxylation of the Centrosomal Protein Cep192
title_sort phd1 links cell-cycle progression to oxygen sensing through hydroxylation of the centrosomal protein cep192
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3757158/
https://www.ncbi.nlm.nih.gov/pubmed/23932902
http://dx.doi.org/10.1016/j.devcel.2013.06.014
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