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

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Dunajová, Lucia ; Cash, Emily ; Markus, Robert ; Rochette, Sophie ; Townley, Amelia R. ; Wheatley, Sally P. (2016)
  • Publisher: The Company of Biologists Ltd
  • Journal: Journal of Cell Science, volume 129, issue 14, pages 2,707-2,712 (issn: 0021-9533, eissn: 1477-9137)
  • Related identifiers: doi: 10.1242/jcs.183277, pmc: PMC4958295
  • Subject: 132 | Survivin | Src | 127 | Mitochondria | Cancer | Short Report

ABSTRACT Survivin (also known as BIRC5) is a cancer-associated protein that exists in several locations in the cell. Its cytoplasmic residence in interphase cells is governed by CRM1 (also known as XPO1)-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 ten amino acids at the N-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 this decapeptide regulates the tyrosine kinase Src, leading to reduced focal adhesion plaques and disruption of F-actin organisation. This strongly suggests that the N-terminus of survivin is a mitochondrial-targeting sequence that regulates Src, and that survivin acts in concert with Src to promote tumorigenesis.
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