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

Aljaberi, Aysha M.; Webster, Jamie R.M.; Wheatley, Sally P.

Authors

Aysha M. Aljaberi

Jamie R.M. Webster

Sally P. Wheatley



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.

Journal Article Type Article
Journal Cancer Cell International
Electronic ISSN 1475-2867
Publisher Springer Verlag
Peer Reviewed Peer Reviewed
Volume 14
Article Number 78
APA6 Citation Aljaberi, A. M., Webster, J. R., & Wheatley, S. P. (in press). Analysis of the functional repertoire of a mutant form of survivin, K129E, which has been linked to lung cancer. Cancer Cell International, 14, https://doi.org/10.1186/s12935-014-0078-8
DOI https://doi.org/10.1186/s12935-014-0078-8
Keywords Survivin, Borealin, Mitosis, Cytokinesis, Apoptosis, Cancer, Polymorphism
Publisher URL http://cancerci.biomedcentral.com/articles/10.1186/s12935-014-0078-8
Related Public URLs http://www.cancerci.com/content/14/1/78
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0





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