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Updated: May 26, 2026
14:28
Peptide-based Identification of Functional Motifs and their Binding Partners
Published on: June 30, 2013
Withanone binds to mortalin and abrogates mortalin-p53 complex: computational and experimental evidence
Abhinav Grover1, Didik Priyandoko, Ran Gao
1Department of Biochemical Engineering & Biotechnology, Indian Institute of Technology Delhi, Hauz Khas, New Delhi 110016, India.
The International Journal of Biochemistry & Cell Biology
|December 14, 2011
Summary
Withanone disrupts the mortalin-p53 interaction, reactivating the p53 tumor suppressor. This finding offers a new strategy for developing targeted cancer therapies with reduced toxicity.
Area of Science:
- Molecular biology
- Biochemistry
- Cancer research
Background:
- Mortalin sequesters the p53 tumor suppressor protein in the cytoplasm, inhibiting its functions and promoting cancer.
- Reactivating p53 by disrupting the mortalin-p53 interaction is a potential cancer therapy strategy.
Purpose of the Study:
- To investigate the in silico interaction of withanone with mortalin.
- To provide experimental evidence for withanone's ability to abrogate the mortalin-p53 complex and restore p53 function in cancer cells.
Main Methods:
- In silico molecular docking and dynamic simulations of withanone-mortalin interactions.
- Experimental validation of mortalin-p53 complex disruption and p53 nuclear translocation in human cancer cells.
Main Results:
- Withanone binds to mortalin in a critical p53-binding region.
- Molecular dynamics simulations confirm the stability of the withanone-mortalin complex.
- Withanone treatment leads to the dissociation of the mortalin-p53 complex, p53 nuclear translocation, and functional reactivation.
Conclusions:
- Withanone effectively disrupts the mortalin-p53 interaction, reactivating p53 in cancer cells.
- This study establishes a molecular basis for developing mortalin-targeting anticancer drugs with potentially lower toxicity.
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