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dc.contributor.authorArmata, Heather L.
dc.contributor.authorShroff, Punita
dc.contributor.authorGarlick, David S.
dc.contributor.authorPenta, Krista L.
dc.contributor.authorTapper, Andrew R.
dc.contributor.authorSluss, Hayla Karen
dc.date2022-08-11T08:09:40.000
dc.date.accessioned2022-08-23T16:39:50Z
dc.date.available2022-08-23T16:39:50Z
dc.date.issued2011-09-27
dc.date.submitted2012-09-06
dc.identifier.citation<p>Armata HL, Shroff P, Garlick DE, Penta K, Tapper AR, et al. (2011) Loss of <em>p53 Ser18</em> and <em>Atm</em> Results in Embryonic Lethality without Cooperation in Tumorigenesis. PLoS ONE 6(9): e24813. doi:10.1371/journal.pone.0024813. <a href="http://dx.doi.org/10.1371/journal.pone.0024813" target="_blank">Link to article on publisher's site</a></p>
dc.identifier.issn1932-6203 (Linking)
dc.identifier.doi10.1371/journal.pone.0024813
dc.identifier.pmid21980358
dc.identifier.urihttp://hdl.handle.net/20.500.14038/39559
dc.description.abstractPhosphorylation at murine Serine 18 (human Serine 15) is a critical regulatory process for the tumor suppressor function of p53. p53Ser18 residue is a substrate for ataxia-telangiectasia mutated (ATM) and ATM-related (ATR) protein kinases. Studies of mice with a germ-line mutation that replaces Ser18 with Ala (p53(S18A) mice) have demonstrated that loss of phosphorylation of p53Ser18 leads to the development of tumors, including lymphomas, fibrosarcomas, leukemia and leiomyosarcomas. The predominant lymphoma is B-cell lymphoma, which is in contrast to the lymphomas observed in Atm(-/-) animals. This observation and the fact that multiple kinases phosphorylate p53Ser18 suggest Atm-independent tumor suppressive functions of p53Ser18. Therefore, in order to examine p53Ser18 function in relationship to ATM, we analyzed the lifespan and tumorigenesis of mice with combined mutations in p53Ser18 and Atm. Surprisingly, we observed no cooperation in survival and tumorigenesis in compound p53(S18A) and Atm(-/-) animals. However, we observed embryonic lethality in the compound mutant animals. In addition, the homozygous p53Ser18 mutant allele impacted the weight of Atm(-/-) animals. These studies examine the genetic interaction of p53Ser18 and Atm in vivo. Furthermore, these studies demonstrate a role of p53Ser18 in regulating embryonic survival and motor coordination.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=21980358&dopt=Abstract">Link to Article in PubMed</a></p>
dc.rights<p>Copyright: © 2011 Armata et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</p>
dc.subjectAnimals
dc.subjectCell Cycle Proteins
dc.subjectCell Proliferation
dc.subjectDNA-Binding Proteins
dc.subjectFemale
dc.subjectFibroblasts
dc.subject*Gene Expression Regulation, Neoplastic
dc.subjectGerm-Line Mutation
dc.subjectHumans
dc.subjectMale
dc.subjectMice
dc.subjectMice, Transgenic
dc.subjectModels, Genetic
dc.subjectMutation
dc.subjectPhosphorylation
dc.subjectProtein-Serine-Threonine Kinases
dc.subjectTumor Suppressor Protein p53
dc.subjectTumor Suppressor Proteins
dc.subjectCancer Biology
dc.subjectCell and Developmental Biology
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleLoss of p53 Ser18 and Atm results in embryonic lethality without cooperation in tumorigenesis
dc.typeJournal Article
dc.source.journaltitlePloS one
dc.source.volume6
dc.source.issue9
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=3354&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/2354
dc.identifier.contextkey3299955
refterms.dateFOA2022-08-23T16:39:51Z
html.description.abstract<p>Phosphorylation at murine Serine 18 (human Serine 15) is a critical regulatory process for the tumor suppressor function of p53. p53Ser18 residue is a substrate for ataxia-telangiectasia mutated (ATM) and ATM-related (ATR) protein kinases. Studies of mice with a germ-line mutation that replaces Ser18 with Ala (p53(S18A) mice) have demonstrated that loss of phosphorylation of p53Ser18 leads to the development of tumors, including lymphomas, fibrosarcomas, leukemia and leiomyosarcomas. The predominant lymphoma is B-cell lymphoma, which is in contrast to the lymphomas observed in Atm(-/-) animals. This observation and the fact that multiple kinases phosphorylate p53Ser18 suggest Atm-independent tumor suppressive functions of p53Ser18. Therefore, in order to examine p53Ser18 function in relationship to ATM, we analyzed the lifespan and tumorigenesis of mice with combined mutations in p53Ser18 and Atm. Surprisingly, we observed no cooperation in survival and tumorigenesis in compound p53(S18A) and Atm(-/-) animals. However, we observed embryonic lethality in the compound mutant animals. In addition, the homozygous p53Ser18 mutant allele impacted the weight of Atm(-/-) animals. These studies examine the genetic interaction of p53Ser18 and Atm in vivo. Furthermore, these studies demonstrate a role of p53Ser18 in regulating embryonic survival and motor coordination.</p>
dc.identifier.submissionpathoapubs/2354
dc.contributor.departmentTapper Lab
dc.contributor.departmentDepartment of Psychiatry
dc.contributor.departmentDepartment of Cancer Biology
dc.contributor.departmentDepartment of Medicine, Division of Endocronology and Metabolism
dc.source.pagese24813


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