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Updated: Jun 15, 2026

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Published on: November 2, 2017
ATM is involved in cell-cycle control through the regulation of retinoblastoma protein phosphorylation
Javier G Pizarro1, Jaume Folch, Aurelio Vazquez de la Torre
1Unitat 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.
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 H(2)O(2) 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.
Insights
Ataxia telangiectasia mutated protein (ATM) regulates cell cycle control by modulating retinoblastoma protein (pRb) phosphorylation. This study reveals a novel ATM molecular network impacting cell cycle progression and DNA repair pathways.
Area of Science:
- Molecular Biology
- Cell Biology
- Neuroscience
Background:
- Ataxia telangiectasia mutated (ATM) protein, a PI3K family member, is crucial for DNA double-strand break (DSB) response.
- Understanding ATM's role in cell-cycle regulation is vital for cellular health and disease research.
Purpose of the Study:
- To investigate the function of ATM in cell-cycle control within dopaminergic rat neuroblastoma B65 cells.
- To elucidate the molecular mechanisms by which ATM influences cell-cycle regulators.
Main Methods:
- Pharmacological inhibition of ATM using KU-55933.
- Partial gene silencing of ATM via small interfering RNA (siRNA) transfection.
- Analysis of cell-cycle proteins, including cyclin A, retinoblastoma protein (pRb), and p53.
Main Results:
- ATM inhibition or silencing reduced levels of cyclin A and phosphorylated pRb (Ser780).
- ATM modulation decreased active p53 (Ser15 phosphorylation), Bax, and p21 expression.
- ATM inhibition prevented H(2)O(2)-induced pRb phosphorylation, confirming its role in DSB response.
Conclusions:
- ATM plays a significant role in regulating the cell cycle through the control of pRb phosphorylation.
- A novel molecular network involving ATM in cell-cycle regulation has been identified.
- ATM represents a potential therapeutic target for conditions involving cell-cycle dysregulation.
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