title: The N-terminus of survivin is a mitochondrial-targeting sequence and Src regulator.
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.
authors.affiliation: School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK.
authors.forename: Lucia
authors.initials: L
authors.lastname: Dunajová
authors.affiliation: School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK.
authors.forename: Emily
authors.initials: E
authors.lastname: Cash
authors.affiliation: School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Markus
authors.affiliation: School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK.
authors.forename: Sophie
authors.initials: S
authors.lastname: Rochette
authors.affiliation: School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK.
authors.forename: Amelia R
authors.initials: AR
authors.lastname: Townley
authors.affiliation: School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK sally.wheatley@nottingham.ac.uk.
authors.forename: Sally P
authors.identifier: 0000-0002-9550-8979
authors.initials: SP
authors.lastname: Wheatley
mesh_terms: D000595:Amino Acid Sequence; D002448:Cell Adhesion; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000737:chemistry* / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D021382:Protein Sorting Signals; D013329:Structure-Activity Relationship; D000077022:Survivin; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D021382:Protein Sorting Signals; D000077022:Survivin; D049452:Green Fluorescent Proteins; D019061:src-Family Kinases
keywords: Cancer; Mitochondria; Src; Survivin