Regulation of ATM/p53-dependent suppression of myc-induced lymphomas by Wip1 phosphatase

Shreeram, Sathyavageeswaran; Hee, Weng Kee; Demidov, Oleg N.; Kek, Calvina; Yamaguchi, Hiroshi; Fornace, Albert J.; Anderson, Carl W.; Appella, Ettore; Bulavin, Dmitry V.

doi:10.1084/jem.20061563

Regulation of ATM/p53-dependent suppression of myc-induced lymphomas by Wip1 phosphatase

Journal Article · Mon Dec 11 00:00:00 EST 2006 · Journal of Experimental Medicine

DOI:https://doi.org/10.1084/jem.20061563· OSTI ID:1625190

Shreeram, Sathyavageeswaran ^[1]; Hee, Weng Kee ^[2]; Demidov, Oleg N. ^[2]; Kek, Calvina ^[2]; Yamaguchi, Hiroshi ^[3]; Fornace, Albert J. ^[4]; Anderson, Carl W. ^[5]; Appella, Ettore ^[3]; Bulavin, Dmitry V. ^[2]

Institute of Molecular and Cell Biology (Singapore); DOE/OSTI
Institute of Molecular and Cell Biology (Singapore)
National Institutes of Health (NIH), Bethesda, MD (United States). National Cancer Institute (NCI)
Harvard School of Public Health, Boston, MA (United States)
Brookhaven National Laboratory (BNL), Upton, NY (United States)

The ataxia telangiectasia mutated (ATM) kinase is a key tumor suppressor that regulates numerous cell cycle checkpoints as well as apoptosis. Here, we report that ATM is a critical player in the regulation of apoptosis and lymphomagenesis in the presence of c-myc. In turn, deletion of the inhibitory ATM phosphatase, Wip1, results in ATM up-regulation and suppression of Eμ-myc–induced B cell lymphomas. Using mouse genetic crosses, we show that the onset of myc-induced lymphomas is dramatically delayed in Wip1-null mice in an ATM- and p53-, but not p38 MAPK– or Arf-, dependent manner. We propose that Wip1 phosphatase is critical for regulating the ATM-mediated tumor surveillance network.

View Accepted Manuscript (DOE)

Research Organization:: Brookhaven National Laboratory (BNL), Upton, NY (United States)

Sponsoring Organization:: Agency for Science, Technology and Research; National Institutes of Health (NIH); USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division

Grant/Contract Number:: SC0012704

OSTI ID:: 1625190

Journal Information:: Journal of Experimental Medicine, Journal Name: Journal of Experimental Medicine Journal Issue: 13 Vol. 203; ISSN 0022-1007

Publisher:: Rockefeller University PressCopyright Statement

Country of Publication:: United States

Language:: English

References (28)

Atm-Deficient Mice: A Paradigm of Ataxia Telangiectasia Barlow, Carrolee; Hirotsune, Shinji; Paylor, Richard Cell, Vol. 86, Issue 1 https://doi.org/10.1016/s0092-8674(00)80086-0	journal	July 1996
Substrate Specificity of the Human Protein Phosphatase 2Cδ, Wip1 Yamaguchi, Hiroshi; Minopoli, Giuseppina; Demidov, Oleg N. Biochemistry, Vol. 44, Issue 14 https://doi.org/10.1021/bi0476634	journal	March 2005
The c-myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice Adams, J. M.; Harris, A. W.; Pinkert, C. A. Nature, Vol. 318, Issue 6046 https://doi.org/10.1038/318533a0	journal	December 1985
Cell-cycle checkpoints and cancer Kastan, Michael B.; Bartek, Jiri Nature, Vol. 432, Issue 7015 https://doi.org/10.1038/nature03097	journal	November 2004
Role of genomic instability and p53 in AID-induced c-myc–Igh translocations Ramiro, Almudena R.; Jankovic, Mila; Callen, Elsa Nature, Vol. 440, Issue 7080 https://doi.org/10.1038/nature04495	journal	January 2006
Autophosphorylation at serine 1987 is dispensable for murine Atm activation in vivo Pellegrini, Manuela; Celeste, Arkady; Difilippantonio, Simone Nature, Vol. 443, Issue 7108 https://doi.org/10.1038/nature05112	journal	August 2006
Amplification of PPM1D in human tumors abrogates p53 tumor-suppressor activity Bulavin, Dmitry V.; Demidov, Oleg N.; Saito, Shin'ichi Nature Genetics, Vol. 31, Issue 2 https://doi.org/10.1038/ng894	journal	May 2002
Regulation of the antioncogenic Chk2 kinase by the oncogenic Wip1 phosphatase Fujimoto, H.; Onishi, N.; Kato, N. Cell Death & Differentiation, Vol. 13, Issue 7 https://doi.org/10.1038/sj.cdd.4401801	journal	November 2005
Autophosphorylation of ataxia-telangiectasia mutated is regulated by protein phosphatase 2A Goodarzi, Aaron A.; Jonnalagadda, Jyoti C.; Douglas, Pauline The EMBO Journal, Vol. 23, Issue 22 https://doi.org/10.1038/sj.emboj.7600455	journal	October 2004
Involvement of novel autophosphorylation sites in ATM activation Kozlov, Sergei V.; Graham, Mark E.; Peng, Cheng The EMBO Journal, Vol. 25, Issue 15 https://doi.org/10.1038/sj.emboj.7601231	journal	July 2006
Bim is a suppressor of Myc-induced mouse B cell leukemia Egle, A.; Harris, A. W.; Bouillet, P. Proceedings of the National Academy of Sciences, Vol. 101, Issue 16 https://doi.org/10.1073/pnas.0401471101	journal	April 2004
p53-inducible Wip1 phosphatase mediates a negative feedback regulation of p38 MAPK-p53 signaling in response to UV radiation Takekawa, M. The EMBO Journal, Vol. 19, Issue 23 https://doi.org/10.1093/emboj/19.23.6517	journal	December 2000
PPM1D dephosphorylates Chk1 and p53 and abrogates cell cycle checkpoints Lu, X. Genes & Development, Vol. 19, Issue 10 https://doi.org/10.1101/gad.1291305	journal	May 2005
Disruption of the ARF-Mdm2-p53 tumor suppressor pathway in Myc-induced lymphomagenesis Eischen, C. M.; Weber, J. D.; Roussel, M. F. Genes & Development, Vol. 13, Issue 20 https://doi.org/10.1101/gad.13.20.2658	journal	October 1999
INK4a/ARF mutations accelerate lymphomagenesis and promote chemoresistance by disabling p53 Schmitt, C. A.; McCurrach, M. E.; de Stanchina, E. Genes & Development, Vol. 13, Issue 20 https://doi.org/10.1101/gad.13.20.2670	journal	October 1999
Cleavage and Inactivation of ATM during Apoptosis Smith, Graeme C. M.; d’adda di Fagagna, Fabrizio; Lakin, Nicholas D. Molecular and Cellular Biology, Vol. 19, Issue 9 https://doi.org/10.1128/mcb.19.9.6076	journal	September 1999
ATM: Genome stability, neuronal development, and cancer cross paths Shiloh, Yosef; Kastan, Michael B. Advances in Cancer Research https://doi.org/10.1016/S0065-230X(01)83007-4	book	January 2001
Atm-Deficient Mice: A Paradigm of Ataxia Telangiectasia Barlow, Carrolee; Hirotsune, Shinji; Paylor, Richard Cell, Vol. 86, Issue 1 https://doi.org/10.1016/S0092-8674(00)80086-0	journal	July 1996
Wip1 Phosphatase Modulates ATM-Dependent Signaling Pathways Shreeram, Sathyavageeswaran; Demidov, Oleg N.; Hee, Weng Kee Molecular Cell, Vol. 23, Issue 5 https://doi.org/10.1016/j.molcel.2006.07.010	journal	September 2006
DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis Bartkova, Jirina; Hořejší, Zuzana; Koed, Karen Nature, Vol. 434, Issue 7035 https://doi.org/10.1038/nature03482	journal	April 2005
Inactivation of the Wip1 phosphatase inhibits mammary tumorigenesis through p38 MAPK–mediated activation of the p16Ink4a-p19Arf pathway Bulavin, Dmitry V.; Phillips, Crissy; Nannenga, Bonnie Nature Genetics, Vol. 36, Issue 4 https://doi.org/10.1038/ng1317	journal	February 2004
Oncogenic properties of PPM1D located within a breast cancer amplification epicenter at 17q23 Li, Jing; Yang, Ying; Peng, Yue Nature Genetics, Vol. 31, Issue 2 https://doi.org/10.1038/ng888	journal	May 2002
Caspases and mitochondria in c-Myc-induced apoptosis: identification of ATM as a new target of caspases Hotti, Anneli; Järvinen, Kristiina; Siivola, Pirjo Oncogene, Vol. 19, Issue 19 https://doi.org/10.1038/sj.onc.1203567	journal	May 2000
ATM activity contributes to the tumor-suppressing functions of p14ARF Li, Yanxia; Wu, Dongcheng; Chen, Biao Oncogene, Vol. 23, Issue 44 https://doi.org/10.1038/sj.onc.1207957	journal	July 2004
ATP Activates Ataxia-Telangiectasia Mutated (ATM) in Vitro Kozlov, Sergei; Gueven, Nuri; Keating, Katherine Journal of Biological Chemistry, Vol. 278, Issue 11 https://doi.org/10.1074/jbc.M300003200	journal	March 2003
p14ARF Activates a Tip60-Dependent and p53-Independent ATM/ATR/CHK Pathway in Response to Genotoxic Stress Eymin, Béatrice; Claverie, Paule; Salon, Caroline Molecular and Cellular Biology, Vol. 26, Issue 11 https://doi.org/10.1128/MCB.02240-05	journal	June 2006
Cleavage and Inactivation of ATM during Apoptosis Smith, Graeme C. M.; d’adda di Fagagna, Fabrizio; Lakin, Nicholas D. Molecular and Cellular Biology, Vol. 19, Issue 9 https://doi.org/10.1128/MCB.19.9.6076	journal	September 1999
E2F1 Uses the ATM Signaling Pathway to Induce p53 and Chk2 Phosphorylation and Apoptosis Powers, John T.; Hong, SungKi; Mayhew, Christopher N. Molecular Cancer Research, Vol. 2, Issue 4 https://doi.org/10.1158/1541-7786.203.2.4	journal	April 2004

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Wip1 phosphatase: between p53 and MAPK kinases pathways Goloudina, Anastasia R.; Kochetkova, Elena Y.; Pospelova, Tatyana V. Oncotarget, Vol. 7, Issue 21 https://doi.org/10.18632/oncotarget.7325	journal	February 2016
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The ATM signaling network in development and disease Stracker, Travis H.; Roig, Ignasi; Knobel, Philip A. Frontiers in Genetics, Vol. 4 https://doi.org/10.3389/fgene.2013.00037	journal	January 2013
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DNA damage-induced regulatory interplay between DAXX, p53, ATM kinase and Wip1 phosphatase Brazina, Jan; Svadlenka, Jan; Macurek, Libor Taylor & Francis https://doi.org/10.6084/m9.figshare.1301973.v1	audiovisual	January 2015
DNA damage-induced regulatory interplay between DAXX, p53, ATM kinase and Wip1 phosphatase Brazina, Jan; Svadlenka, Jan; Macurek, Libor Taylor & Francis https://doi.org/10.6084/m9.figshare.1301973.v2	audiovisual	January 2015
DNA damage-induced regulatory interplay between DAXX, p53, ATM kinase and Wip1 phosphatase Brazina, Jan; Svadlenka, Jan; Macurek, Libor Taylor & Francis https://doi.org/10.6084/m9.figshare.1301973.v4	audiovisual	January 2015

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