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.

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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