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dc.contributor.author
Giono, Luciana Eugenia
dc.contributor.author
Resnick Silverman, Lois
dc.contributor.author
Carvajal, Luis A.
dc.contributor.author
St. Clair, Selvon
dc.contributor.author
Manfredi, James J.
dc.date.available
2018-12-04T14:06:10Z
dc.date.issued
2017-06
dc.identifier.citation
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
dc.identifier.issn
0950-9232
dc.identifier.uri
http://hdl.handle.net/11336/65696
dc.description.abstract
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.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Nature Publishing Group
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Mdm2
dc.subject
Cdc25c
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P53
dc.subject
Proteasome
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Degradation
dc.subject
Cell Cycle
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Otras Ciencias Biológicas
dc.subject.classification
Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
Mdm2 promotes Cdc25C protein degradation and delays cell cycle progression through the G2/M phase
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-10-23T18:09:48Z
dc.journal.volume
36
dc.journal.number
49
dc.journal.pagination
6762-6773
dc.journal.pais
Reino Unido
dc.journal.ciudad
Londres
dc.description.fil
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
dc.description.fil
Fil: Resnick Silverman, Lois. Icahn School Of Medicine At Mount Sinai; Estados Unidos
dc.description.fil
Fil: Carvajal, Luis A.. Icahn School Of Medicine At Mount Sinai; Estados Unidos
dc.description.fil
Fil: St. Clair, Selvon. Icahn School Of Medicine At Mount Sinai; Estados Unidos
dc.description.fil
Fil: Manfredi, James J.. Icahn School Of Medicine At Mount Sinai; Estados Unidos
dc.journal.title
Oncogene
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1038/onc.2017.254
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