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Updated: Dec 21, 2025

Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins
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Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins

Published on: September 28, 2012

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TFEB Modulates p21/WAF1/CIP1 during the DNA Damage Response

Sandra Pisonero-Vaquero1, Chiara Soldati1, Marcella Cesana1,2

  • 1Telethon Institute of Genetics and Medicine (TIGEM), High Content Screening Facility, Via Campi Flegrei 34, 80078 Pozzuoli, Italy.

Cells
|May 14, 2020
PubMed

Insights

Transcription factor EB (TFEB) directly regulates p21 expression, impacting cell survival during DNA damage. Targeting this TFEB-p21 pathway may offer new cancer treatment strategies.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Cellular Metabolism

Background:

  • The MiT/TFE family of transcription factors (MITF, TFE3, TFEB) are key regulators of autophagy and lysosome biogenesis.
  • These factors influence energy metabolism and cancer cell survival under stress.

Purpose of the Study:

  • To investigate the role of transcription factor EB (TFEB) in regulating p21/WAF1 expression.
  • To determine TFEB's involvement in the DNA damage response (DDR).

Main Methods:

  • TFEB depletion and overexpression experiments.
  • Doxorubicin treatment to induce DNA damage.
  • Cell cycle analysis (G2/M phase arrest).
  • Pharmacological inhibition of p21.

Main Results:

  • TFEB depletion reduced basal p21/WAF1 expression.
  • TFEB overexpression increased p21 in a p53-dependent manner.
  • TFEB mediated p21 activation upon DNA damage, delaying cell cycle arrest and promoting survival.
  • p21 inhibition abolished TFEB-mediated protection during DDR.

Conclusions:

  • TFEB directly regulates p21 expression in steady-state and during DNA damage response.
  • The TFEB-p21 pathway plays a crucial role in cancer cell survival under genotoxic stress.
  • Targeting the TFEB-p21 axis presents a potential therapeutic strategy for cancer treatment.
Keywords:
DNA-damage responseTFEBautophagycancercell cycledoxorubicingenotoxic stressp21

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