Analysis of the functional repertoire of a mutant form of survivin, K129E, which has been linked to lung cancer

Aljaberi, Aysha M. and Webster, Jamie R.M. and Wheatley, Sally P. (2014) Analysis of the functional repertoire of a mutant form of survivin, K129E, which has been linked to lung cancer. Cancer Cell International, 14 . 78/1-78/8. ISSN 1475-2867

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Abstract

Background

Survivin is a protein that is normally present only in G2 and M-phases in somatic cells, however, in cancer cells, it is expressed throughout the cell cycle. A prosurvival factor, survivin is both an inhibitor of apoptosis and an essential mitotic protein, thus it has attracted much attention as a target for new oncotherapies. Despite its prevalence in cancer, reports of survivin mutations have mostly been restricted to loci within its promoter, which increase the abundance of the protein. To date the only published mutation within the coding sequence is an adenine > guanine substitution in exon 4. This polymorphism, which was found in a cohort of Korean lung cancer patients, causes a lysine > glutamic acid mutation (K129E) in the protein. However, whether it plays a causative role in cancer has not been addressed.

Methods

Using site directed mutagenesis we recapitulate K129E expression in cultured human cells and assess its anti-apoptotic and mitotic activities.

Results

K129E retains its anti-apoptotic activity, but causes errors in mitosis and cytokinesis, which may be linked to its reduced affinity for borealin.

Conclusion

K129E expression can induce genomic instability by introducing mitotic aberrations, thus it may play a causative role in cancer.

Item Type: Article
Keywords: Survivin, Borealin, Mitosis, Cytokinesis, Apoptosis, Cancer, Polymorphism
Schools/Departments: University of Nottingham UK Campus > Faculty of Medicine and Health Sciences > School of Life Sciences > School of Biomedical Sciences
Identification Number: https://doi.org/10.1186/s12935-014-0078-8
Related URLs:
URLURL Type
http://www.cancerci.com/content/14/1/78UNSPECIFIED
Depositing User: Wheatley, Sally
Date Deposited: 14 Jul 2016 12:00
Last Modified: 15 Sep 2016 09:28
URI: http://eprints.nottingham.ac.uk/id/eprint/35004

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