Send to

Choose Destination
See comment in PubMed Commons below
Int J Biochem Cell Biol. 2012 Mar;44(3):496-504. doi: 10.1016/j.biocel.2011.11.021. Epub 2011 Dec 2.

Withanone binds to mortalin and abrogates mortalin-p53 complex: computational and experimental evidence.

Author information

Department of Biochemical Engineering & Biotechnology, Indian Institute of Technology Delhi, Hauz Khas, New Delhi 110016, India.


Mortalin binds to p53 tumor suppressor protein and sequesters it in the cytoplasm. This results in an inhibition of the transcriptional activation and control of centrosome duplication functions of p53, thus contributing to human carcinogenesis. Abrogation of mortalin-p53 interaction and reactivation of p53 function could be a valid proposition for cancer therapy. In the present study, we first investigated in silico the interaction of withanone, a withanolide with anticancer activity, with mortalin. We found that withanone could bind to mortalin in a region, earlier predicted critical for binding to p53. Cationic rhodacyanine dye, MKT-077 has also shown to bind the same region and kill cancer cells selectively. We report the molecular dynamic simulations revealing the thermodynamic and structural stability of the withanone-mortalin complexes. We also demonstrate the experimental evidence of abrogation of mortalin-p53 complex by withanone resulting in nuclear translocation and functional reactivation of p53 in human cancer cells. The present study establishes a molecular interaction basis that could be used for screening and development of anticancer drugs with low toxicity to normal cells. Accurate knowledge of the 3D structure of mortalin would further enhance the potential of such analyses to understand the molecular basis of mortalin biology and mortalin based cancer therapy.

[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center