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dc.contributor.authorDohi, Takehiko
dc.contributor.authorBeltrami, Elena
dc.contributor.authorWall, Nathan R.
dc.contributor.authorPlescia, Janet
dc.contributor.authorAltieri, Dario C.
dc.date2022-08-11T08:10:05.000
dc.date.accessioned2022-08-23T16:55:13Z
dc.date.available2022-08-23T16:55:13Z
dc.date.issued2004-10-19
dc.date.submitted2008-10-31
dc.identifier.citationJ Clin Invest. 2004 Oct;114(8):1117-27. <a href="http://dx.doi.org/10.1172/JCI22222">Link to article on publisher's site</a>
dc.identifier.issn0021-9738 (Print)
dc.identifier.doi10.1172/JCI22222
dc.identifier.pmid15489959
dc.identifier.urihttp://hdl.handle.net/20.500.14038/42669
dc.description.abstractEvasion 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.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=15489959&dopt=Abstract">Link to Article in PubMed</a>
dc.subjectAnimals
dc.subjectApoptosis
dc.subjectCaspases
dc.subjectCell Hypoxia
dc.subjectCell Line, Tumor
dc.subjectEndopeptidase K
dc.subjectEnzyme Activation
dc.subjectEnzyme Inhibitors
dc.subjectHela Cells
dc.subjectHumans
dc.subjectIn Situ Nick-End Labeling
dc.subjectMicrotubule-Associated Proteins
dc.subjectMitochondria
dc.subjectNeoplasm Proteins
dc.subjectNeoplasms
dc.subjectRecombinant Fusion Proteins
dc.subjectStaurosporine
dc.subjectSubcellular Fractions
dc.subjectCancer Biology
dc.titleMitochondrial survivin inhibits apoptosis and promotes tumorigenesis
dc.typeJournal Article
dc.source.journaltitleThe Journal of clinical investigation
dc.source.volume114
dc.source.issue8
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1995&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/996
dc.identifier.contextkey659179
refterms.dateFOA2022-08-23T16:55:13Z
html.description.abstract<p>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.</p>
dc.identifier.submissionpathoapubs/996
dc.contributor.departmentDepartment of Cancer Biology and the Cancer Center
dc.source.pages1117-27


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