Mdm2 promotes Cdc25C protein degradation and delays cell cycle progression through the G2/M phase

Autores
Giono, Luciana Eugenia; Resnick Silverman, Lois; Carvajal, Luis A.; St. Clair, Selvon; Manfredi, James J.
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Upon different types of stress, the gene encoding the mitosis-promoting phosphatase Cdc25C is transcriptionally repressed by p53, contributing to p53’s enforcement of a G2 cell cycle arrest. In addition, Cdc25C protein stability is also decreased following DNA damage. Mdm2, another p53 target gene, encodes a ubiquitin ligase that negatively regulates p53 levels by ubiquitination. Ablation of Mdm2 by siRNA led to an increase in p53 protein and repression of Cdc25C gene expression. However, Cdc25C protein levels were actually increased following Mdm2 depletion. Mdm2 is shown to negatively regulate Cdc25C protein levels by reducing its half-life independently of the presence of p53. Further, Mdm2 physically interacts with Cdc25C and promotes its degradation through the proteasome in a ubiquitin-independent manner. Either Mdm2 overexpression or Cdc25C downregulation delays cell cycle progression through the G2/M phase. Thus, the repression of the Cdc25C promoter by p53, together with p53-dependent induction of Mdm2 and subsequent degradation of Cdc25C, could provide a dual mechanism by which p53 can enforce and maintain a G2/M cell cycle arrest.
Fil: Giono, Luciana Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Resnick Silverman, Lois. Icahn School Of Medicine At Mount Sinai; Estados Unidos
Fil: Carvajal, Luis A.. Icahn School Of Medicine At Mount Sinai; Estados Unidos
Fil: St. Clair, Selvon. Icahn School Of Medicine At Mount Sinai; Estados Unidos
Fil: Manfredi, James J.. Icahn School Of Medicine At Mount Sinai; Estados Unidos
Materia
MDM2
CDC25C
P53
PROTEASOME
DEGRADATION
CELL CYCLE
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/65696
Acceder
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network_acronym_str CONICETDig
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network_name_str CONICET Digital (CONICET)
spelling Mdm2 promotes Cdc25C protein degradation and delays cell cycle progression through the G2/M phaseGiono, Luciana EugeniaResnick Silverman, LoisCarvajal, Luis A.St. Clair, SelvonManfredi, James J.MDM2CDC25CP53PROTEASOMEDEGRADATIONCELL CYCLEhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Upon different types of stress, the gene encoding the mitosis-promoting phosphatase Cdc25C is transcriptionally repressed by p53, contributing to p53’s enforcement of a G2 cell cycle arrest. In addition, Cdc25C protein stability is also decreased following DNA damage. Mdm2, another p53 target gene, encodes a ubiquitin ligase that negatively regulates p53 levels by ubiquitination. Ablation of Mdm2 by siRNA led to an increase in p53 protein and repression of Cdc25C gene expression. However, Cdc25C protein levels were actually increased following Mdm2 depletion. Mdm2 is shown to negatively regulate Cdc25C protein levels by reducing its half-life independently of the presence of p53. Further, Mdm2 physically interacts with Cdc25C and promotes its degradation through the proteasome in a ubiquitin-independent manner. Either Mdm2 overexpression or Cdc25C downregulation delays cell cycle progression through the G2/M phase. Thus, the repression of the Cdc25C promoter by p53, together with p53-dependent induction of Mdm2 and subsequent degradation of Cdc25C, could provide a dual mechanism by which p53 can enforce and maintain a G2/M cell cycle arrest.Fil: Giono, Luciana Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Resnick Silverman, Lois. Icahn School Of Medicine At Mount Sinai; Estados UnidosFil: Carvajal, Luis A.. Icahn School Of Medicine At Mount Sinai; Estados UnidosFil: St. Clair, Selvon. Icahn School Of Medicine At Mount Sinai; Estados UnidosFil: Manfredi, James J.. Icahn School Of Medicine At Mount Sinai; Estados UnidosNature Publishing Group2017-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/65696Giono, Luciana Eugenia; Resnick Silverman, Lois; Carvajal, Luis A.; St. Clair, Selvon; Manfredi, James J.; Mdm2 promotes Cdc25C protein degradation and delays cell cycle progression through the G2/M phase; Nature Publishing Group; Oncogene; 36; 49; 6-2017; 6762-67730950-9232CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1038/onc.2017.254info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:06:34Zoai:ri.conicet.gov.ar:11336/65696instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-10 13:06:35.081CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Mdm2 promotes Cdc25C protein degradation and delays cell cycle progression through the G2/M phase
title Mdm2 promotes Cdc25C protein degradation and delays cell cycle progression through the G2/M phase
spellingShingle Mdm2 promotes Cdc25C protein degradation and delays cell cycle progression through the G2/M phase
Giono, Luciana Eugenia
MDM2
CDC25C
P53
PROTEASOME
DEGRADATION
CELL CYCLE
title_short Mdm2 promotes Cdc25C protein degradation and delays cell cycle progression through the G2/M phase
title_full Mdm2 promotes Cdc25C protein degradation and delays cell cycle progression through the G2/M phase
title_fullStr Mdm2 promotes Cdc25C protein degradation and delays cell cycle progression through the G2/M phase
title_full_unstemmed Mdm2 promotes Cdc25C protein degradation and delays cell cycle progression through the G2/M phase
title_sort Mdm2 promotes Cdc25C protein degradation and delays cell cycle progression through the G2/M phase
dc.creator.none.fl_str_mv Giono, Luciana Eugenia
Resnick Silverman, Lois
Carvajal, Luis A.
St. Clair, Selvon
Manfredi, James J.
author Giono, Luciana Eugenia
author_facet Giono, Luciana Eugenia
Resnick Silverman, Lois
Carvajal, Luis A.
St. Clair, Selvon
Manfredi, James J.
author_role author
author2 Resnick Silverman, Lois
Carvajal, Luis A.
St. Clair, Selvon
Manfredi, James J.
author2_role author
author
author
author
dc.subject.none.fl_str_mv MDM2
CDC25C
P53
PROTEASOME
DEGRADATION
CELL CYCLE
topic MDM2
CDC25C
P53
PROTEASOME
DEGRADATION
CELL CYCLE
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Upon different types of stress, the gene encoding the mitosis-promoting phosphatase Cdc25C is transcriptionally repressed by p53, contributing to p53’s enforcement of a G2 cell cycle arrest. In addition, Cdc25C protein stability is also decreased following DNA damage. Mdm2, another p53 target gene, encodes a ubiquitin ligase that negatively regulates p53 levels by ubiquitination. Ablation of Mdm2 by siRNA led to an increase in p53 protein and repression of Cdc25C gene expression. However, Cdc25C protein levels were actually increased following Mdm2 depletion. Mdm2 is shown to negatively regulate Cdc25C protein levels by reducing its half-life independently of the presence of p53. Further, Mdm2 physically interacts with Cdc25C and promotes its degradation through the proteasome in a ubiquitin-independent manner. Either Mdm2 overexpression or Cdc25C downregulation delays cell cycle progression through the G2/M phase. Thus, the repression of the Cdc25C promoter by p53, together with p53-dependent induction of Mdm2 and subsequent degradation of Cdc25C, could provide a dual mechanism by which p53 can enforce and maintain a G2/M cell cycle arrest.
Fil: Giono, Luciana Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Resnick Silverman, Lois. Icahn School Of Medicine At Mount Sinai; Estados Unidos
Fil: Carvajal, Luis A.. Icahn School Of Medicine At Mount Sinai; Estados Unidos
Fil: St. Clair, Selvon. Icahn School Of Medicine At Mount Sinai; Estados Unidos
Fil: Manfredi, James J.. Icahn School Of Medicine At Mount Sinai; Estados Unidos
description Upon different types of stress, the gene encoding the mitosis-promoting phosphatase Cdc25C is transcriptionally repressed by p53, contributing to p53’s enforcement of a G2 cell cycle arrest. In addition, Cdc25C protein stability is also decreased following DNA damage. Mdm2, another p53 target gene, encodes a ubiquitin ligase that negatively regulates p53 levels by ubiquitination. Ablation of Mdm2 by siRNA led to an increase in p53 protein and repression of Cdc25C gene expression. However, Cdc25C protein levels were actually increased following Mdm2 depletion. Mdm2 is shown to negatively regulate Cdc25C protein levels by reducing its half-life independently of the presence of p53. Further, Mdm2 physically interacts with Cdc25C and promotes its degradation through the proteasome in a ubiquitin-independent manner. Either Mdm2 overexpression or Cdc25C downregulation delays cell cycle progression through the G2/M phase. Thus, the repression of the Cdc25C promoter by p53, together with p53-dependent induction of Mdm2 and subsequent degradation of Cdc25C, could provide a dual mechanism by which p53 can enforce and maintain a G2/M cell cycle arrest.
publishDate 2017
dc.date.none.fl_str_mv 2017-06
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/65696
Giono, Luciana Eugenia; Resnick Silverman, Lois; Carvajal, Luis A.; St. Clair, Selvon; Manfredi, James J.; Mdm2 promotes Cdc25C protein degradation and delays cell cycle progression through the G2/M phase; Nature Publishing Group; Oncogene; 36; 49; 6-2017; 6762-6773
0950-9232
CONICET Digital
CONICET
url http://hdl.handle.net/11336/65696
identifier_str_mv Giono, Luciana Eugenia; Resnick Silverman, Lois; Carvajal, Luis A.; St. Clair, Selvon; Manfredi, James J.; Mdm2 promotes Cdc25C protein degradation and delays cell cycle progression through the G2/M phase; Nature Publishing Group; Oncogene; 36; 49; 6-2017; 6762-6773
0950-9232
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1038/onc.2017.254
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.993085

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