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http://purl.uniprot.org/citations/12704195http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/12704195http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/12704195http://www.w3.org/2000/01/rdf-schema#comment"15-Lipoxygenase 2 (15-LOX2), the most abundant arachidonate (AA)-metabolizing enzyme expressed in adult human prostate, is a negative cell-cycle regulator in normal human prostate epithelial cells. Here we study the subcellular distribution of 15-LOX2 and report its tumor-suppressive functions. Immunocytochemistry and biochemical fractionation reveal that 15-LOX2 is expressed at multiple subcellular locations, including cytoplasm, cytoskeleton, cell-cell border, and nucleus. Surprisingly, the three splice variants of 15-LOX2 we previously cloned, i.e. 15-LOX2sv-a/b/c, are mostly excluded from the nucleus. A potential bi-partite nuclear localization signal (NLS),203RKGLWRSLNEMKRIFNFRR221, is identified in the N terminus of 15-LOX2, which is retained in all splice variants. Site-directed mutagenesis reveals that this putative NLS is only partially involved in the nuclear import of 15-LOX2. To elucidate the relationship between nuclear localization, enzymatic activity, and tumor suppressive functions, we established PCa cell clones stably expressing 15-LOX2 or 15-LOX2sv-b. The 15-LOX2 clones express 15-LOX2 in the nuclei and possess robust enzymatic activity, whereas 15-LOX2sv-b clones show neither nuclear protein localization nor AA-metabolizing activity. To our surprise, both 15-LOX2- and 15-LOX2sv-b-stable clones proliferate much slower in vitro when compared with control clones. More importantly, when orthotopically implanted in nude mouse prostate, both 15-LOX2 and 15-LOX2sv-b suppress PC3 tumor growth in vivo. Together, these results suggest that both 15-LOX2 and 15-LOX2sv-b suppress prostate tumor development, and the tumor-suppressive functions apparently do not necessarily depend on AA-metabolizing activity and nuclear localization."xsd:string
http://purl.uniprot.org/citations/12704195http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m301920200"xsd:string
http://purl.uniprot.org/citations/12704195http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m301920200"xsd:string
http://purl.uniprot.org/citations/12704195http://purl.uniprot.org/core/author"Tang S."xsd:string
http://purl.uniprot.org/citations/12704195http://purl.uniprot.org/core/author"Tang S."xsd:string
http://purl.uniprot.org/citations/12704195http://purl.uniprot.org/core/author"Yang P."xsd:string
http://purl.uniprot.org/citations/12704195http://purl.uniprot.org/core/author"Yang P."xsd:string
http://purl.uniprot.org/citations/12704195http://purl.uniprot.org/core/author"Newman R.A."xsd:string
http://purl.uniprot.org/citations/12704195http://purl.uniprot.org/core/author"Newman R.A."xsd:string
http://purl.uniprot.org/citations/12704195http://purl.uniprot.org/core/author"Chopra D."xsd:string
http://purl.uniprot.org/citations/12704195http://purl.uniprot.org/core/author"Chopra D."xsd:string
http://purl.uniprot.org/citations/12704195http://purl.uniprot.org/core/author"Chandra D."xsd:string
http://purl.uniprot.org/citations/12704195http://purl.uniprot.org/core/author"Chandra D."xsd:string
http://purl.uniprot.org/citations/12704195http://purl.uniprot.org/core/author"Tang D.G."xsd:string
http://purl.uniprot.org/citations/12704195http://purl.uniprot.org/core/author"Tang D.G."xsd:string
http://purl.uniprot.org/citations/12704195http://purl.uniprot.org/core/author"Klein R.D."xsd:string
http://purl.uniprot.org/citations/12704195http://purl.uniprot.org/core/author"Klein R.D."xsd:string
http://purl.uniprot.org/citations/12704195http://purl.uniprot.org/core/author"Shappell S.B."xsd:string
http://purl.uniprot.org/citations/12704195http://purl.uniprot.org/core/author"Shappell S.B."xsd:string
http://purl.uniprot.org/citations/12704195http://purl.uniprot.org/core/author"Bhatia B."xsd:string
http://purl.uniprot.org/citations/12704195http://purl.uniprot.org/core/author"Bhatia B."xsd:string
http://purl.uniprot.org/citations/12704195http://purl.uniprot.org/core/author"Maldonado C.J."xsd:string
http://purl.uniprot.org/citations/12704195http://purl.uniprot.org/core/author"Maldonado C.J."xsd:string