Journal of Cellular Biochemistry

ATM is involved in cell-cycle control through the regulation of retinoblastoma protein phosphorylation

Authors

  • Javier G. Pizarro,

    1. Unitat de Farmacologia i Farmacognosia, Institut de Biomedicina (IBUB), Centro deInvestigacion Biomedica en Red de Enfermedades Neurodegenerativas (CIBERNED), Facultat de Farmacia, Universitat de Barcelona, Nucli Universitari de Pedralbes, Barcelona E-08028, Spain
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  • Jaume Folch,

    1. Unitat de Bioquimica, Facultat de Medicina i Ciencies de la Salut, Centro de Investigacion Biomedica en Red de Enfermedades Neurodegenerativas (CIBERNED), Universitat Rovira i Virgili, C./St. Llorenc 21, Reus E-43201 (Tarragona), Spain
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  • Aurelio Vazquez de la Torre,

    1. Unitat de Farmacologia i Farmacognosia, Institut de Biomedicina (IBUB), Centro deInvestigacion Biomedica en Red de Enfermedades Neurodegenerativas (CIBERNED), Facultat de Farmacia, Universitat de Barcelona, Nucli Universitari de Pedralbes, Barcelona E-08028, Spain
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  • Felix Junyent,

    1. Unitat de Farmacologia i Farmacognosia, Institut de Biomedicina (IBUB), Centro deInvestigacion Biomedica en Red de Enfermedades Neurodegenerativas (CIBERNED), Facultat de Farmacia, Universitat de Barcelona, Nucli Universitari de Pedralbes, Barcelona E-08028, Spain
    2. Unitat de Bioquimica, Facultat de Medicina i Ciencies de la Salut, Centro de Investigacion Biomedica en Red de Enfermedades Neurodegenerativas (CIBERNED), Universitat Rovira i Virgili, C./St. Llorenc 21, Reus E-43201 (Tarragona), Spain
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  • Ester Verdaguer,

    1. Unitat de Farmacologia i Farmacognosia, Institut de Biomedicina (IBUB), Centro deInvestigacion Biomedica en Red de Enfermedades Neurodegenerativas (CIBERNED), Facultat de Farmacia, Universitat de Barcelona, Nucli Universitari de Pedralbes, Barcelona E-08028, Spain
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  • Joaquin Jordan,

    1. Facultad de Medicina, Departamento de Ciencias Medicas, Universidad de Castilla-La, Mancha, Avda. Almansa, 14, Albacete E-02006, Spain
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  • Merce Pallas,

    1. Unitat de Farmacologia i Farmacognosia, Institut de Biomedicina (IBUB), Centro deInvestigacion Biomedica en Red de Enfermedades Neurodegenerativas (CIBERNED), Facultat de Farmacia, Universitat de Barcelona, Nucli Universitari de Pedralbes, Barcelona E-08028, Spain
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    • Senior co-author.

  • Antoni Camins

    Corresponding author
    1. Unitat de Farmacologia i Farmacognosia, Institut de Biomedicina (IBUB), Centro deInvestigacion Biomedica en Red de Enfermedades Neurodegenerativas (CIBERNED), Facultat de Farmacia, Universitat de Barcelona, Nucli Universitari de Pedralbes, Barcelona E-08028, Spain
    • Unitat de Farmacologia i Farmacognosia i Institut de Biomedicina, Facultat de Farmacia, Universitat de Barcelona, Nucli Universitari de Pedralbes, E-08028 Barcelona, Spain.
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    • Senior co-author.


  • Javier G. Pizarro and Jaume Folch contributed equally to this work.

Abstract

Ataxia telangiectasia mutated protein (ATM) is a member of the phosphatidylinositol-3 kinase (PI3K) family, which has a role in the cellular response to DNA double-strand breaks (DSBs). In the present study, we evaluated the role of ATM in cell-cycle control in dopaminergic rat neuroblastoma B65 cells. For this purpose, ATM activity was either inhibited pharmacologically with the specific inhibitor KU-55933, or the ATM gene was partially silenced by transfection with small interfering RNA (siRNA). Our data indicate that although ATM inhibition did not affect the cell cycle, both treatments specifically decreased the levels of cyclin A and retinoblastoma protein (pRb), phosphorylated at Ser780. Furthermore, ATM inhibition decreased the active form of p53, which is phosphorylated at Ser15, and also decreased Bax and p21 expression. Using H2O2 as a positive control of DSBs, caused a rapid pRb phosphorylation, this was prevented by KU-55933 and siRNA treatment. Collectively, our data demonstrate how a new molecular network on ATM regulates the cell cycle through the control of pRb phosphorylation. These findings support a new target of ATM. J. Cell. Biochem. 110: 210–218, 2010. © 2010 Wiley-Liss, Inc.

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