Polycomb protein SCML2 regulates the cell cycle by binding and modulating CDK/CYCLIN/p21 complexes.

Polycomb group (PcG) proteins are transcriptional repressors of genes involved in development and differentiation, and also maintain repression of key genes involved in the cell cycle, indirectly regulating cell proliferation. The human SCML2 gene, a mammalian homologue of the Drosophila PcG protein...

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Autores principales: Emilio Lecona, Luis Alejandro Rojas, Roberto Bonasio, Andrew Johnston, Oscar Fernández-Capetillo, Danny Reinberg
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Publicado: Public Library of Science (PLoS) 2013
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Acceso en línea:https://doaj.org/article/d4ddbaaa48fc4b02b8abd870469d19f8
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spelling oai:doaj.org-article:d4ddbaaa48fc4b02b8abd870469d19f82021-11-18T05:37:41ZPolycomb protein SCML2 regulates the cell cycle by binding and modulating CDK/CYCLIN/p21 complexes.1544-91731545-788510.1371/journal.pbio.1001737https://doaj.org/article/d4ddbaaa48fc4b02b8abd870469d19f82013-12-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24358021/?tool=EBIhttps://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885Polycomb group (PcG) proteins are transcriptional repressors of genes involved in development and differentiation, and also maintain repression of key genes involved in the cell cycle, indirectly regulating cell proliferation. The human SCML2 gene, a mammalian homologue of the Drosophila PcG protein SCM, encodes two protein isoforms: SCML2A that is bound to chromatin and SCML2B that is predominantly nucleoplasmic. Here, we purified SCML2B and found that it forms a stable complex with CDK/CYCLIN/p21 and p27, enhancing the inhibitory effect of p21/p27. SCML2B participates in the G1/S checkpoint by stabilizing p21 and favoring its interaction with CDK2/CYCE, resulting in decreased kinase activity and inhibited progression through G1. In turn, CDK/CYCLIN complexes phosphorylate SCML2, and the interaction of SCML2B with CDK2 is regulated through the cell cycle. These findings highlight a direct crosstalk between the Polycomb system of cellular memory and the cell-cycle machinery in mammals.Emilio LeconaLuis Alejandro RojasRoberto BonasioAndrew JohnstonOscar Fernández-CapetilloDanny ReinbergPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 11, Iss 12, p e1001737 (2013)
institution DOAJ
collection DOAJ
language EN
topic Biology (General)
QH301-705.5
spellingShingle Biology (General)
QH301-705.5
Emilio Lecona
Luis Alejandro Rojas
Roberto Bonasio
Andrew Johnston
Oscar Fernández-Capetillo
Danny Reinberg
Polycomb protein SCML2 regulates the cell cycle by binding and modulating CDK/CYCLIN/p21 complexes.
description Polycomb group (PcG) proteins are transcriptional repressors of genes involved in development and differentiation, and also maintain repression of key genes involved in the cell cycle, indirectly regulating cell proliferation. The human SCML2 gene, a mammalian homologue of the Drosophila PcG protein SCM, encodes two protein isoforms: SCML2A that is bound to chromatin and SCML2B that is predominantly nucleoplasmic. Here, we purified SCML2B and found that it forms a stable complex with CDK/CYCLIN/p21 and p27, enhancing the inhibitory effect of p21/p27. SCML2B participates in the G1/S checkpoint by stabilizing p21 and favoring its interaction with CDK2/CYCE, resulting in decreased kinase activity and inhibited progression through G1. In turn, CDK/CYCLIN complexes phosphorylate SCML2, and the interaction of SCML2B with CDK2 is regulated through the cell cycle. These findings highlight a direct crosstalk between the Polycomb system of cellular memory and the cell-cycle machinery in mammals.
format article
author Emilio Lecona
Luis Alejandro Rojas
Roberto Bonasio
Andrew Johnston
Oscar Fernández-Capetillo
Danny Reinberg
author_facet Emilio Lecona
Luis Alejandro Rojas
Roberto Bonasio
Andrew Johnston
Oscar Fernández-Capetillo
Danny Reinberg
author_sort Emilio Lecona
title Polycomb protein SCML2 regulates the cell cycle by binding and modulating CDK/CYCLIN/p21 complexes.
title_short Polycomb protein SCML2 regulates the cell cycle by binding and modulating CDK/CYCLIN/p21 complexes.
title_full Polycomb protein SCML2 regulates the cell cycle by binding and modulating CDK/CYCLIN/p21 complexes.
title_fullStr Polycomb protein SCML2 regulates the cell cycle by binding and modulating CDK/CYCLIN/p21 complexes.
title_full_unstemmed Polycomb protein SCML2 regulates the cell cycle by binding and modulating CDK/CYCLIN/p21 complexes.
title_sort polycomb protein scml2 regulates the cell cycle by binding and modulating cdk/cyclin/p21 complexes.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/d4ddbaaa48fc4b02b8abd870469d19f8
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