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

Dunajova, Lucia and Cash, Emily and Markus, Robert and Rochette, Sophie and Townley, Amelia R. and Wheatley, Sally P. (2016) The N-terminus of survivin is a mitochondrial-targeting sequence and Src regulator. Journal of Cell Science, 129 . pp. 2707-2712. ISSN 1477-9137

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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.

Item Type: Article
Keywords: Survivin; C-Src; Mitochondria; Cancer
Schools/Departments: University of Nottingham UK Campus > Faculty of Medicine and Health Sciences > School of Life Sciences
Identification Number: https://doi.org/10.1242/jcs.183277
Depositing User: Eprints, Support
Date Deposited: 13 Jun 2016 07:43
Last Modified: 13 Sep 2016 16:17
URI: http://eprints.nottingham.ac.uk/id/eprint/33585

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