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dc.contributor.authorGannon, Hugh S.
dc.contributor.authorWoda, Bruce A.
dc.contributor.authorJones, Stephen N.
dc.date2022-08-11T08:09:15.000
dc.date.accessioned2022-08-23T16:23:59Z
dc.date.available2022-08-23T16:23:59Z
dc.date.issued2012-05-15
dc.date.submitted2012-10-02
dc.identifier.citationCancer Cell. 2012 May 15;21(5):668-79. <a href="http://dx.doi.org/10.1016/j.ccr.2012.04.011">Link to article on publisher's site</a>
dc.identifier.issn1535-6108 (Linking)
dc.identifier.doi10.1016/j.ccr.2012.04.011
dc.identifier.urihttp://hdl.handle.net/20.500.14038/36023
dc.description.abstractDNA damage induced by ionizing radiation activates the ATM kinase, which subsequently stabilizes and activates the p53 tumor suppressor protein. Although phosphorylation of p53 by ATM was found previously to modulate p53 levels and transcriptional activities in vivo, it does not appear to be a major regulator of p53 stability. We have utilized mice bearing altered Mdm2 alleles to demonstrate that ATM phosphorylation of Mdm2 serine 394 is required for robust p53 stabilization and activation after DNA damage. In addition, we demonstrate that dephosphorylation of Mdm2 Ser394 regulates attenuation of the p53-mediated response to DNA damage. Therefore, the phosphorylation status of Mdm2 Ser394 governs p53 protein levels and functions in cells undergoing DNA damage.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=22624716&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1016/j.ccr.2012.04.011
dc.subjectAnimals
dc.subjectApoptosis
dc.subjectCell Cycle Proteins
dc.subject*DNA Damage
dc.subjectDNA-Binding Proteins
dc.subjectEnzyme Activation
dc.subjectIntestine, Small
dc.subjectMice
dc.subjectMice, 129 Strain
dc.subjectMice, Inbred C57BL
dc.subjectMutation, Missense
dc.subjectPhosphorylation
dc.subjectProtein Stability
dc.subjectProtein-Serine-Threonine Kinases
dc.subjectProto-Oncogene Proteins c-mdm2
dc.subjectRadiation Tolerance
dc.subjectSerine
dc.subjectSpleen
dc.subjectThymus Gland
dc.subjectTime Factors
dc.subjectTumor Suppressor Protein p53
dc.subjectTumor Suppressor Proteins
dc.subjectCell and Developmental Biology
dc.subjectCell Biology
dc.titleATM phosphorylation of Mdm2 Ser394 regulates the amplitude and duration of the DNA damage response in mice
dc.typeJournal Article
dc.source.journaltitleCancer cell
dc.source.volume21
dc.source.issue5
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/jones/27
dc.identifier.contextkey3363704
html.description.abstract<p>DNA damage induced by ionizing radiation activates the ATM kinase, which subsequently stabilizes and activates the p53 tumor suppressor protein. Although phosphorylation of p53 by ATM was found previously to modulate p53 levels and transcriptional activities in vivo, it does not appear to be a major regulator of p53 stability. We have utilized mice bearing altered Mdm2 alleles to demonstrate that ATM phosphorylation of Mdm2 serine 394 is required for robust p53 stabilization and activation after DNA damage. In addition, we demonstrate that dephosphorylation of Mdm2 Ser394 regulates attenuation of the p53-mediated response to DNA damage. Therefore, the phosphorylation status of Mdm2 Ser394 governs p53 protein levels and functions in cells undergoing DNA damage.</p>
dc.identifier.submissionpathjones/27
dc.contributor.departmentDepartment of Pathology
dc.contributor.departmentDepartment of Cell and Developmental Biology
dc.source.pages668-79


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