Abstract
Stress protein mortalin is a multifunctional protein and is highly expressed in cancers. It has been shown to interact with tumor suppressor protein-p53 (both wild and mutant types) and inactivates its transcriptional activation and apoptotic functions in cancer cells. In the present study, we found that, unlike most of the cancer cells, HepG2 hepatoma lacked mortalin–p53 interaction. We demonstrate that the mortalin–p53 interaction exists in cancer cells that are either physiologically stressed (frequently associated with p53 mutations) or treated with stress-inducing chemicals. Targeting mortalin–p53 interaction with either mortalin small hairpin RNA or a chemical or peptide inhibitor could induce p53-mediated tumor cell-specific apoptosis in hepatocellular carcinoma; p53-null hepatoma or normal hepatocytes remain unaffected.
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Accession codes
Abbreviations
- shRNA:
-
small hairpin RNA
- Hsp70:
-
heat shock protein 70
- HCC:
-
hepatocellular carcinoma
- GRP78:
-
glucose-regulated protein 78
- MKT-077:
-
1-ethyl-2-[[3-ethyl-5-(3-methylbenzothiazolin-2-yliden)]-4-oxothiazolidin-2-ylidenemethyl]pyridinium chloride
- MTT:
-
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide
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Acknowledgements
This work was supported in part by the grants from the NUS seed fund, NMRC grant from the Ministry of Health, Singapore, and grant from the National Institute of Advanced Industrial Science & Technology (AIST).
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Lu, WJ., Lee, N., Kaul, S. et al. Mortalin–p53 interaction in cancer cells is stress dependent and constitutes a selective target for cancer therapy. Cell Death Differ 18, 1046–1056 (2011). https://doi.org/10.1038/cdd.2010.177
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DOI: https://doi.org/10.1038/cdd.2010.177
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