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Updated: Dec 21, 2025
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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
Summary
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.
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