Journal
JOURNAL OF CELL SCIENCE
Volume 129, Issue 14, Pages 2707-2712Publisher
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.183277
Keywords
Survivin; Src; Mitochondria; Cancer
Categories
Funding
- Biotechnology and Biological Sciences Research Council [BB/F016956/1]
- Biotechnology and Biological Sciences Research Council [BB/L013827/1] Funding Source: researchfish
- BBSRC [BB/L013827/1] Funding Source: UKRI
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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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