{"@context":"http://iiif.io/api/presentation/2/context.json","@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/manifest.json","@type":"sc:Manifest","label":"The identification of guanosine-5'-triphosphate binding protein 2 (GTPBP2) as a potential drug target for diseases involving excessive Wnt signaling","metadata":[{"label":"dc.description.sponsorship","value":"This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree."},{"label":"dc.format","value":"Monograph"},{"label":"dc.format.medium","value":"Electronic Resource"},{"label":"dc.identifier.uri","value":"http://hdl.handle.net/11401/76935"},{"label":"dc.language.iso","value":"en_US"},{"label":"dc.publisher","value":"The Graduate School, Stony Brook University: Stony Brook, NY."},{"label":"dcterms.abstract","value":"Canonical Wnt signaling is involved in the regulation of many cellular behaviors dependent upon context, including the induction of cell proliferation, promotion of cell survival, repression of apoptosis, and regulation of cell differentiation. Perturbations in the Wnt signaling pathway have been shown to be present in a various amount of human diseases, such as cancers of the colon and breast, leading to aberrant cellular activity. As such, recent studies have focused on the inhibition of the Wnt signaling pathway in hopes of restoring normal cellular behaviors in diseases with excessive Wnt signaling activity. Our lab has discovered that the large GTPase, guanosine-5'-triphosphate binding protein 2 (Gtpbp2), is essential for Wnt signaling, axis formation, and induction of organizer gene expression in Xenopus embryos, demonstrating that Gtpbp2 negatively regulates cytoplasmic Axin protein levels, a rate limiting component of the β -catenin destruction complex. The goal of this research was to investigate the mammalian homolog GTPBP2 to determine if its pivotal role in Wnt signaling expands to mammalian species. Co-immunoprecipitation assays in Hek293t cells revealed physical interactions between GTPBP2 and Axin and glycogen synthase kinase β (GSK3B), and in order to determine the effects of GTPBP2 knockdown in mammalian cells, GTPBP2 shRNAi expressing Hek293t cells were generated using lentiviral infection. As many cancer related Wnt signaling pathway mutations require low Axin protein levels, the determination whether GTPBP2 has a negative regulatory effect on Axin in mammalian cells may reveal the possibility that inhibitors of GTPBP2 might serve as a potential therapeutic for these Wnt-related diseases."},{"label":"dcterms.available","value":"2017-09-20T16:51:28Z"},{"label":"dcterms.contributor","value":"Thomsen, Gerald H."},{"label":"dcterms.creator","value":"Wyrick, Jonathan Manit"},{"label":"dcterms.dateAccepted","value":"2017-09-20T16:51:28Z"},{"label":"dcterms.dateSubmitted","value":"2017-09-20T16:51:28Z"},{"label":"dcterms.description","value":"Department of Biochemistry and Cell Biology."},{"label":"dcterms.extent","value":"41 pg."},{"label":"dcterms.format","value":"Monograph"},{"label":"dcterms.identifier","value":"http://hdl.handle.net/11401/76935"},{"label":"dcterms.issued","value":"2014-12-01"},{"label":"dcterms.language","value":"en_US"},{"label":"dcterms.provenance","value":"Made available in DSpace on 2017-09-20T16:51:28Z (GMT). No. of bitstreams: 1\nWyrick_grad.sunysb_0771M_12111.pdf: 3276688 bytes, checksum: f45bdc3746db20029e7475dca83d324d (MD5)\n  Previous issue date:    1"},{"label":"dcterms.publisher","value":"The Graduate School, Stony Brook University: Stony Brook, NY."},{"label":"dcterms.subject","value":"Biochemistry"},{"label":"dcterms.title","value":"The identification of guanosine-5'-triphosphate binding protein 2 (GTPBP2) as a potential drug target for diseases involving excessive Wnt signaling"},{"label":"dcterms.type","value":"Thesis"},{"label":"dc.type","value":"Thesis"}],"description":"This manifest was generated dynamically","viewingDirection":"left-to-right","sequences":[{"@type":"sc:Sequence","canvases":[{"@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/canvas/page-1.json","@type":"sc:Canvas","label":"Page 1","height":1650,"width":1275,"images":[{"@type":"oa:Annotation","motivation":"sc:painting","resource":{"@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/35%2F54%2F81%2F35548151734173567496089467846256610025/full/full/0/default.jpg","@type":"dctypes:Image","format":"image/jpeg","height":1650,"width":1275,"service":{"@context":"http://iiif.io/api/image/2/context.json","@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/35%2F54%2F81%2F35548151734173567496089467846256610025","profile":"http://iiif.io/api/image/2/level2.json"}},"on":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/canvas/page-1.json"}]}]}]}