Cargando…
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...
Autores principales: | , , , , , , , , |
---|---|
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 |
_version_ | 1782282174943199232 |
---|---|
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. |
format | Online Article Text |
id | pubmed-3757158 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT mosersandrac phd1linkscellcycleprogressiontooxygensensingthroughhydroxylationofthecentrosomalproteincep192 AT bensaddekdalila phd1linkscellcycleprogressiontooxygensensingthroughhydroxylationofthecentrosomalproteincep192 AT ortmannbrian phd1linkscellcycleprogressiontooxygensensingthroughhydroxylationofthecentrosomalproteincep192 AT maurejeanfrancois phd1linkscellcycleprogressiontooxygensensingthroughhydroxylationofthecentrosomalproteincep192 AT mudiesharon phd1linkscellcycleprogressiontooxygensensingthroughhydroxylationofthecentrosomalproteincep192 AT blowjjulian phd1linkscellcycleprogressiontooxygensensingthroughhydroxylationofthecentrosomalproteincep192 AT lamondangusi phd1linkscellcycleprogressiontooxygensensingthroughhydroxylationofthecentrosomalproteincep192 AT swedlowjasonr phd1linkscellcycleprogressiontooxygensensingthroughhydroxylationofthecentrosomalproteincep192 AT rochasonia phd1linkscellcycleprogressiontooxygensensingthroughhydroxylationofthecentrosomalproteincep192 |