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Proteomic Landscape of Tissue-Specific Cyclin E Functions in Vivo

E-type cyclins (cyclins E1 and E2) are components of the cell cycle machinery that has been conserved from yeast to humans. The major function of E-type cyclins is to drive cell division. It is unknown whether in addition to their ‘core’ cell cycle functions, E-type cyclins also perform unique tissu...

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Autores principales: Odajima, Junko, Saini, Siddharth, Jung, Piotr, Ndassa-Colday, Yasmine, Ficaro, Scott, Geng, Yan, Marco, Eugenio, Michowski, Wojciech, Wang, Yaoyu E., DeCaprio, James A., Litovchick, Larisa, Marto, Jarrod, Sicinski, Piotr
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5102403/
https://www.ncbi.nlm.nih.gov/pubmed/27828963
http://dx.doi.org/10.1371/journal.pgen.1006429
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author Odajima, Junko
Saini, Siddharth
Jung, Piotr
Ndassa-Colday, Yasmine
Ficaro, Scott
Geng, Yan
Marco, Eugenio
Michowski, Wojciech
Wang, Yaoyu E.
DeCaprio, James A.
Litovchick, Larisa
Marto, Jarrod
Sicinski, Piotr
author_facet Odajima, Junko
Saini, Siddharth
Jung, Piotr
Ndassa-Colday, Yasmine
Ficaro, Scott
Geng, Yan
Marco, Eugenio
Michowski, Wojciech
Wang, Yaoyu E.
DeCaprio, James A.
Litovchick, Larisa
Marto, Jarrod
Sicinski, Piotr
author_sort Odajima, Junko
collection PubMed
description E-type cyclins (cyclins E1 and E2) are components of the cell cycle machinery that has been conserved from yeast to humans. The major function of E-type cyclins is to drive cell division. It is unknown whether in addition to their ‘core’ cell cycle functions, E-type cyclins also perform unique tissue-specific roles. Here, we applied high-throughput mass spectrometric analyses of mouse organs to define the repertoire of cyclin E protein partners in vivo. We found that cyclin E interacts with distinct sets of proteins in different compartments. These cyclin E interactors are highly enriched for phosphorylation targets of cyclin E and its catalytic partner, the cyclin-dependent kinase 2 (Cdk2). Among cyclin E interactors we identified several novel tissue-specific substrates of cyclin E-Cdk2 kinase. In proliferating compartments, cyclin E-Cdk2 phosphorylates Lin proteins within the DREAM complex. In the testes, cyclin E-Cdk2 phosphorylates Mybl1 and Dmrtc2, two meiotic transcription factors that represent key regulators of spermatogenesis. In embryonic and adult brains cyclin E interacts with proteins involved in neurogenesis, while in adult brains also with proteins regulating microtubule-based processes and microtubule cytoskeleton. We also used quantitative proteomics to demonstrate re-wiring of the cyclin E interactome upon ablation of Cdk2. This approach can be used to study how protein interactome changes during development or in any pathological state such as aging or cancer.
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spelling pubmed-51024032016-11-18 Proteomic Landscape of Tissue-Specific Cyclin E Functions in Vivo Odajima, Junko Saini, Siddharth Jung, Piotr Ndassa-Colday, Yasmine Ficaro, Scott Geng, Yan Marco, Eugenio Michowski, Wojciech Wang, Yaoyu E. DeCaprio, James A. Litovchick, Larisa Marto, Jarrod Sicinski, Piotr PLoS Genet Research Article E-type cyclins (cyclins E1 and E2) are components of the cell cycle machinery that has been conserved from yeast to humans. The major function of E-type cyclins is to drive cell division. It is unknown whether in addition to their ‘core’ cell cycle functions, E-type cyclins also perform unique tissue-specific roles. Here, we applied high-throughput mass spectrometric analyses of mouse organs to define the repertoire of cyclin E protein partners in vivo. We found that cyclin E interacts with distinct sets of proteins in different compartments. These cyclin E interactors are highly enriched for phosphorylation targets of cyclin E and its catalytic partner, the cyclin-dependent kinase 2 (Cdk2). Among cyclin E interactors we identified several novel tissue-specific substrates of cyclin E-Cdk2 kinase. In proliferating compartments, cyclin E-Cdk2 phosphorylates Lin proteins within the DREAM complex. In the testes, cyclin E-Cdk2 phosphorylates Mybl1 and Dmrtc2, two meiotic transcription factors that represent key regulators of spermatogenesis. In embryonic and adult brains cyclin E interacts with proteins involved in neurogenesis, while in adult brains also with proteins regulating microtubule-based processes and microtubule cytoskeleton. We also used quantitative proteomics to demonstrate re-wiring of the cyclin E interactome upon ablation of Cdk2. This approach can be used to study how protein interactome changes during development or in any pathological state such as aging or cancer. Public Library of Science 2016-11-09 /pmc/articles/PMC5102403/ /pubmed/27828963 http://dx.doi.org/10.1371/journal.pgen.1006429 Text en © 2016 Odajima et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Odajima, Junko
Saini, Siddharth
Jung, Piotr
Ndassa-Colday, Yasmine
Ficaro, Scott
Geng, Yan
Marco, Eugenio
Michowski, Wojciech
Wang, Yaoyu E.
DeCaprio, James A.
Litovchick, Larisa
Marto, Jarrod
Sicinski, Piotr
Proteomic Landscape of Tissue-Specific Cyclin E Functions in Vivo
title Proteomic Landscape of Tissue-Specific Cyclin E Functions in Vivo
title_full Proteomic Landscape of Tissue-Specific Cyclin E Functions in Vivo
title_fullStr Proteomic Landscape of Tissue-Specific Cyclin E Functions in Vivo
title_full_unstemmed Proteomic Landscape of Tissue-Specific Cyclin E Functions in Vivo
title_short Proteomic Landscape of Tissue-Specific Cyclin E Functions in Vivo
title_sort proteomic landscape of tissue-specific cyclin e functions in vivo
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5102403/
https://www.ncbi.nlm.nih.gov/pubmed/27828963
http://dx.doi.org/10.1371/journal.pgen.1006429
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