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

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...

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Autores principales: Shreeram, Sathyavageeswaran, Hee, Weng Kee, Demidov, Oleg N., Kek, Calvina, Yamaguchi, Hiroshi, Fornace, Albert J., Anderson, Carl W., Appella, Ettore, Bulavin, Dmitry V.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2006
Materias:
Brief Definitive Reports
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118180/
https://www.ncbi.nlm.nih.gov/pubmed/17158963
http://dx.doi.org/10.1084/jem.20061563
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author Shreeram, Sathyavageeswaran
Hee, Weng Kee
Demidov, Oleg N.
Kek, Calvina
Yamaguchi, Hiroshi
Fornace, Albert J.
Anderson, Carl W.
Appella, Ettore
Bulavin, Dmitry V.
author_facet Shreeram, Sathyavageeswaran
Hee, Weng Kee
Demidov, Oleg N.
Kek, Calvina
Yamaguchi, Hiroshi
Fornace, Albert J.
Anderson, Carl W.
Appella, Ettore
Bulavin, Dmitry V.
author_sort Shreeram, Sathyavageeswaran
collection PubMed
description 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.
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spelling pubmed-21181802007-12-13 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. J Exp Med Brief Definitive Reports 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. The Rockefeller University Press 2006-12-25 /pmc/articles/PMC2118180/ /pubmed/17158963 http://dx.doi.org/10.1084/jem.20061563 Text en Copyright © 2006, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Brief Definitive Reports
Shreeram, Sathyavageeswaran
Hee, Weng Kee
Demidov, Oleg N.
Kek, Calvina
Yamaguchi, Hiroshi
Fornace, Albert J.
Anderson, Carl W.
Appella, Ettore
Bulavin, Dmitry V.
Regulation of ATM/p53-dependent suppression of myc-induced lymphomas by Wip1 phosphatase
title Regulation of ATM/p53-dependent suppression of myc-induced lymphomas by Wip1 phosphatase
title_full Regulation of ATM/p53-dependent suppression of myc-induced lymphomas by Wip1 phosphatase
title_fullStr Regulation of ATM/p53-dependent suppression of myc-induced lymphomas by Wip1 phosphatase
title_full_unstemmed Regulation of ATM/p53-dependent suppression of myc-induced lymphomas by Wip1 phosphatase
title_short Regulation of ATM/p53-dependent suppression of myc-induced lymphomas by Wip1 phosphatase
title_sort regulation of atm/p53-dependent suppression of myc-induced lymphomas by wip1 phosphatase
topic Brief Definitive Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118180/
https://www.ncbi.nlm.nih.gov/pubmed/17158963
http://dx.doi.org/10.1084/jem.20061563
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