Loss of p53 Ser18 and Atm results in embryonic lethality without cooperation in tumorigenesis
Authors
Armata, Heather L.Shroff, Punita
Garlick, David S.
Penta, Krista L.
Tapper, Andrew R.
Sluss, Hayla Karen
UMass Chan Affiliations
Tapper LabDepartment of Psychiatry
Department of Cancer Biology
Department of Medicine, Division of Endocronology and Metabolism
Document Type
Journal ArticlePublication Date
2011-09-27Keywords
AnimalsCell Cycle Proteins
Cell Proliferation
DNA-Binding Proteins
Female
Fibroblasts
*Gene Expression Regulation, Neoplastic
Germ-Line Mutation
Humans
Male
Mice
Mice, Transgenic
Models, Genetic
Mutation
Phosphorylation
Protein-Serine-Threonine Kinases
Tumor Suppressor Protein p53
Tumor Suppressor Proteins
Cancer Biology
Cell and Developmental Biology
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
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.Source
Armata HL, Shroff P, Garlick DE, Penta K, Tapper AR, et al. (2011) Loss of p53 Ser18 and Atm Results in Embryonic Lethality without Cooperation in Tumorigenesis. PLoS ONE 6(9): e24813. doi:10.1371/journal.pone.0024813. Link to article on publisher's site
DOI
10.1371/journal.pone.0024813Permanent Link to this Item
http://hdl.handle.net/20.500.14038/39559PubMed ID
21980358Related Resources
Rights
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.
ae974a485f413a2113503eed53cd6c53
10.1371/journal.pone.0024813
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