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The N-terminus of survivin is a mitochondrial-targeting sequence and Src regulator

Dunajova, Lucia; Cash, Emily; Markus, Robert; Rochette, Sophie; Townley, Amelia R.; Wheatley, Sally P.

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Authors

Lucia Dunajova

Emily Cash

Robert Markus

Sophie Rochette

Amelia R. Townley

Sally P. Wheatley



Abstract

Survivin is a cancer-associated protein that exists in several locations in the cell. Its cytoplasmic residence in interphase cells is governed by CRM1-mediated nuclear exportation, and its localisation during mitosis to the centromeres and midzone microtubules is that of a canonical chromosomal passenger protein. In addition to these well-established locations, survivin is also a mitochondrial protein, but how it gets there and its function therein is presently unclear. Here we show that the first 10 amino acids at the NH2 terminus of survivin are sufficient to target GFP to the mitochondria in vivo, and ectopic expression of this decapeptide decreases cell adhesion and accelerates proliferation. The data support a signalling mechanism in which mitochondrial survivin activates the tyrosine kinase, C-Src, leading to reduced focal adhesion plaques and disruption of F-actin organisation. This strongly suggests that the NH2 terminus of survivin is a mitochondrial targeting sequence that regulates C-Src, and that survivin acts in concert with C-Src to promote tumorigenesis.

Citation

Dunajova, L., Cash, E., Markus, R., Rochette, S., Townley, A. R., & Wheatley, S. P. (in press). The N-terminus of survivin is a mitochondrial-targeting sequence and Src regulator. Journal of Cell Science, 129, https://doi.org/10.1242/jcs.183277

Journal Article Type Article
Acceptance Date May 20, 2016
Online Publication Date May 31, 2016
Deposit Date Jun 13, 2016
Publicly Available Date Jun 13, 2016
Journal Journal of Cell Science
Print ISSN 0021-9533
Electronic ISSN 1477-9137
Publisher Company of Biologists
Peer Reviewed Peer Reviewed
Volume 129
DOI https://doi.org/10.1242/jcs.183277
Keywords Survivin; C-Src; Mitochondria; Cancer
Public URL https://nottingham-repository.worktribe.com/output/787661
Publisher URL http://jcs.biologists.org/content/129/14/2707
Contract Date Jun 13, 2016

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