Mitochondrial survivin inhibits apoptosis and promotes tumorigenesis
UMass Chan Affiliations
Department of Cancer Biology and the Cancer CenterDocument Type
Journal ArticlePublication Date
2004-10-19Keywords
AnimalsApoptosis
Caspases
Cell Hypoxia
Cell Line, Tumor
Endopeptidase K
Enzyme Activation
Enzyme Inhibitors
Hela Cells
Humans
In Situ Nick-End Labeling
Microtubule-Associated Proteins
Mitochondria
Neoplasm Proteins
Neoplasms
Recombinant Fusion Proteins
Staurosporine
Subcellular Fractions
Cancer Biology
Metadata
Show full item recordAbstract
Evasion of apoptosis is a hallmark of cancer, but the molecular circuitries of this process are not understood. Here we show that survivin, a member of the inhibitor of apoptosis gene family that is overexpressed in cancer, exists in a novel mitochondrial pool in tumor cells. In response to cell death stimulation, mitochondrial survivin is rapidly discharged in the cytosol, where it prevents caspase activation and inhibits apoptosis. Selective targeting of survivin to mitochondria enhances colony formation in soft agar, accelerates tumor growth in immunocompromised animals, and abolishes tumor cell apoptosis in vivo. Therefore, mitochondrial survivin orchestrates a novel pathway of apoptosis inhibition, which contributes to tumor progression.Source
J Clin Invest. 2004 Oct;114(8):1117-27. Link to article on publisher's siteDOI
10.1172/JCI22222Permanent Link to this Item
http://hdl.handle.net/20.500.14038/42669PubMed ID
15489959Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1172/JCI22222