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

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

Cancer Cell International, August 2014

25788861

Aysha M Aljaberi, Jamie RM Webster, Sally P Wheatley

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. Using site directed mutagenesis we recapitulate K129E expression in cultured human cells and assess its anti-apoptotic and mitotic activities. K129E retains its anti-apoptotic activity, but causes errors in mitosis and cytokinesis, which may be linked to its reduced affinity for borealin. K129E expression can induce genomic instability by introducing mitotic aberrations, thus it may play a causative role in cancer.