Myc and cell cycle control

Soon after the discovery of the Myc gene (c-Myc), it became clear thatMyc expression levels tightly correlate to cell proliferation. The entry in cell cycle of quiescent cells upon Myc enforced expression has been described in manymodels. Also, the downregulation or inactivation ofMyc results in the...

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Autores: Bretones Sánchez, Gabriel, Delgado Villar, María Dolores|||0000-0003-4682-4040, León Serrano, Javier|||0000-0001-5803-0112
Tipo de recurso: artículo
Fecha de publicación:2015
País:España
Institución:Universidad de Cantabria (UC)
Repositorio:UCrea Repositorio Abierto de la Universidad de Cantabria
Idioma:inglés
OAI Identifier:oai:repositorio.unican.es:10902/9501
Acceso en línea:http://hdl.handle.net/10902/9501
Access Level:acceso abierto
Palabra clave:Myc
Cell cycle
Proliferation
Cyclin
Cdk
p21
p27
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spelling Myc and cell cycle controlBretones Sánchez, GabrielDelgado Villar, María Dolores|||0000-0003-4682-4040León Serrano, Javier|||0000-0001-5803-0112MycCell cycleProliferationCyclinCdkp21p27Soon after the discovery of the Myc gene (c-Myc), it became clear thatMyc expression levels tightly correlate to cell proliferation. The entry in cell cycle of quiescent cells upon Myc enforced expression has been described in manymodels. Also, the downregulation or inactivation ofMyc results in the impairment of cell cycle progression. Given the frequent deregulation of Myc oncogene in human cancer it is important to dissect out the mechanisms underlying the role ofMyc on cell cycle control. Several parallel mechanisms account forMyc-mediated stimulation of the cell cycle. First,most of the critical positive cell cycle regulators are encoded by genes induced byMyc. These Myc target genes include Cdks, cyclins and E2F transcription factors. Apart from its direct effects on the transcription, Myc is able to hyperactivate cyclin/Cdk complexes through the induction of Cdk activating kinase (CAK) and Cdc25 phosphatases. Moreover, Myc antagonizes the activity of cell cycle inhibitors as p21 and p27 through different mechanisms. Thus, Myc is able to block p21 transcription or to induce Skp2, a protein involved in p27 degradation. Finally, Myc induces DNA replication by binding to replication origins and by upregulating genes encoding proteins required for replication initiation. Myc also regulates genes involved in the mitotic control. A promising approach to treat tumors with deregulated Myc is the synthetic lethality based on the inhibition of Cdks. Thus, the knowledge of the Myc-dependent cell cycle regulatory mechanisms will help to discover new therapeutic approaches directed against malignancies with deregulated Myc. This article is part of a Special Issue entitled: Myc proteins in cell biology and pathology.The work in the laboratory of the authors is funded by grants SAF11-23796 from Spanish Ministry of Industry and Innovation, and ISCIII-RETIC RD12/0036/0033 from Spanish Ministry of Health to JL, and FIS 11/00397 to MDD. GB is recipient of a fellowship form the FPI Program. We apologize to colleagues whose work has not been cited in the form of their original papers but in reviews and whose work has not been discussed due to space limitations or unintentional omission.ElsevierUniversidad de Cantabria20152015-01-01journal articlehttp://purl.org/coar/resource_type/c_6501NAhttp://purl.org/coar/version/c_be7fb7dd8ff6fe43info:eu-repo/semantics/articlehttp://hdl.handle.net/10902/9501BIOCHIMICA ET BIOPHYSICA ACTA-Gene Regulatory Mechanisms 2015. 1849: 506-516reponame:UCrea Repositorio Abierto de la Universidad de Cantabriainstname:Universidad de Cantabria (UC)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:repositorio.unican.es:10902/95012026-06-02T12:39:31Z
dc.title.none.fl_str_mv Myc and cell cycle control
title Myc and cell cycle control
spellingShingle Myc and cell cycle control
Bretones Sánchez, Gabriel
Myc
Cell cycle
Proliferation
Cyclin
Cdk
p21
p27
title_short Myc and cell cycle control
title_full Myc and cell cycle control
title_fullStr Myc and cell cycle control
title_full_unstemmed Myc and cell cycle control
title_sort Myc and cell cycle control
dc.creator.none.fl_str_mv Bretones Sánchez, Gabriel
Delgado Villar, María Dolores|||0000-0003-4682-4040
León Serrano, Javier|||0000-0001-5803-0112
author Bretones Sánchez, Gabriel
author_facet Bretones Sánchez, Gabriel
Delgado Villar, María Dolores|||0000-0003-4682-4040
León Serrano, Javier|||0000-0001-5803-0112
author_role author
author2 Delgado Villar, María Dolores|||0000-0003-4682-4040
León Serrano, Javier|||0000-0001-5803-0112
author2_role author
author
dc.contributor.none.fl_str_mv Universidad de Cantabria
dc.subject.none.fl_str_mv Myc
Cell cycle
Proliferation
Cyclin
Cdk
p21
p27
topic Myc
Cell cycle
Proliferation
Cyclin
Cdk
p21
p27
description Soon after the discovery of the Myc gene (c-Myc), it became clear thatMyc expression levels tightly correlate to cell proliferation. The entry in cell cycle of quiescent cells upon Myc enforced expression has been described in manymodels. Also, the downregulation or inactivation ofMyc results in the impairment of cell cycle progression. Given the frequent deregulation of Myc oncogene in human cancer it is important to dissect out the mechanisms underlying the role ofMyc on cell cycle control. Several parallel mechanisms account forMyc-mediated stimulation of the cell cycle. First,most of the critical positive cell cycle regulators are encoded by genes induced byMyc. These Myc target genes include Cdks, cyclins and E2F transcription factors. Apart from its direct effects on the transcription, Myc is able to hyperactivate cyclin/Cdk complexes through the induction of Cdk activating kinase (CAK) and Cdc25 phosphatases. Moreover, Myc antagonizes the activity of cell cycle inhibitors as p21 and p27 through different mechanisms. Thus, Myc is able to block p21 transcription or to induce Skp2, a protein involved in p27 degradation. Finally, Myc induces DNA replication by binding to replication origins and by upregulating genes encoding proteins required for replication initiation. Myc also regulates genes involved in the mitotic control. A promising approach to treat tumors with deregulated Myc is the synthetic lethality based on the inhibition of Cdks. Thus, the knowledge of the Myc-dependent cell cycle regulatory mechanisms will help to discover new therapeutic approaches directed against malignancies with deregulated Myc. This article is part of a Special Issue entitled: Myc proteins in cell biology and pathology.
publishDate 2015
dc.date.none.fl_str_mv 2015
2015-01-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
NA
http://purl.org/coar/version/c_be7fb7dd8ff6fe43
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10902/9501
url http://hdl.handle.net/10902/9501
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv BIOCHIMICA ET BIOPHYSICA ACTA-Gene Regulatory Mechanisms 2015. 1849: 506-516
reponame:UCrea Repositorio Abierto de la Universidad de Cantabria
instname:Universidad de Cantabria (UC)
instname_str Universidad de Cantabria (UC)
reponame_str UCrea Repositorio Abierto de la Universidad de Cantabria
collection UCrea Repositorio Abierto de la Universidad de Cantabria
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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