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Tau affects P53 function and cell fate during the DNA damage response

Martina Sola1,2, Claudia Magrin1,2, Giona Pedrioli1,3

  • 1Neurodegeneration Research Group, Laboratory for Biomedical Neurosciences, Ente Cantonale Ospedaliero, Torricella-Taverne, Switzerland.

Communications Biology
|May 20, 2020
PubMed

Insights

Tau protein depletion impairs DNA damage response, affecting P53 stability and leading to increased cell senescence. This suggests Tau

Area of Science:

  • Molecular Biology
  • Neuroscience
  • Genetics

Background:

  • Cells possess a DNA damage response system regulated by P53.
  • Accumulated DNA damage and aberrant cell fate are implicated in aging-associated disorders like cancer and neurodegeneration.
  • Tauopathies are neurodegenerative diseases characterized by Tau protein aggregation.

Purpose of the Study:

  • To investigate the role of Tau in the cellular response to DNA damage.
  • To examine the impact of Tau depletion on P53 regulation and cell fate.
  • To explore the potential link between Tau, P53, and neurodegeneration.

Main Methods:

  • Studied the response to acute DNA damage in neuroblastoma cells with depleted Tau (loss-of-function model).
  • Assessed P53 stability and activity.
  • Analyzed P53 modification and its interaction with MDM2.

Main Results:

  • Tau depletion resulted in altered P53 stability and activity.
  • Reduced cell death and increased cell senescence were observed in Tau-depleted cells.
  • Tau's function involves regulating P53 modification and MDM2 activity.

Conclusions:

  • Tau plays a critical role in maintaining P53 integrity and function during DNA damage response.
  • Loss of Tau function leads to impaired DNA damage response, promoting cell senescence.
  • These findings offer new insights into the pathomechanisms of neurodegeneration and potential therapeutic strategies.

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