{"@context":"http://iiif.io/api/presentation/2/context.json","@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/manifest.json","@type":"sc:Manifest","label":"Interactions between \u00ce\u00b3-Synuclein and Phospholipase C\u00ce\u00b2 and their effects on Cancer Phenotypes","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/11401/76748"},{"label":"dc.language.iso","value":"en_US"},{"label":"dc.publisher","value":"The Graduate School, Stony Brook University: Stony Brook, NY."},{"label":"dcterms.abstract","value":"\u00ce\u00b3-Synuclein is a protein of neuronal origin that is highly expressed in late-stage human breast cancers, but not in early-stage breast cancers or non-cancerous breast tissues. In model systems, \u00ce\u00b3-synuclein binds strongly to phospholipase C\u00ce\u00b22 (PLC\u00ce\u00b22). PLC\u00ce\u00b22 is activated by heterotrimeric G protein subunits G\u00ce\u00b1q and G\u00ce\u00b2\u00ce\u00b3, and by the small GTPase Rac to generate intracellular calcium signals.  PLC\u00ce\u00b22 is also highly expressed in breast cancer.  In-vitro studies have shown that \u00ce\u00b3-synuclein binds to the same region of PLC\u00ce\u00b22 as G\u00ce\u00b1q.  The work presented in this dissertation reveals a strong binding between \u00ce\u00b3-synuclein and PLC\u00ce\u00b22 in the breast cancer cell line MDA MB 231. In these cells, it was also seen that down-regulation of \u00ce\u00b3-synuclein reduces the protein level of PLC\u00ce\u00b22 while increasing its transcription. \u00ce\u00b3-Synuclein down-regulation also promotes the interaction between G\u00ce\u00b1q and PLC\u00ce\u00b22 increasing the calcium response to G\u00ce\u00b1q agonists. \u00ce\u00b3-Synuclein down-regulation also affects the binding between PLC\u00ce\u00b22 and Rac. This change in association impacts Rac-mediated cell migration as demonstrated by decreased cell migration and invasion and changes in cell morphology.  This dissertation studies the interaction between \u00ce\u00b3-synuclein, PLC\u00ce\u00b22 and PLC\u00ce\u00b22\u00e2\u20ac\u2122s binding partners for the first time in cells. This dissertation corroborates recent evidence that shows that \u00ce\u00b3-synuclein promotes breast cancer cell migration, invasion and proliferation.  The dissertation shows for the first time that these effects are partially mediated by \u00ce\u00b3-synuclein - PLC\u00ce\u00b22 interactions."},{"label":"dcterms.available","value":"2017-09-20T16:51:06Z"},{"label":"dcterms.contributor","value":"Scarlata, Suzanne"},{"label":"dcterms.creator","value":"Yerramilli, Venkata Siddartha Krishna"},{"label":"dcterms.dateAccepted","value":"2017-09-20T16:51:06Z"},{"label":"dcterms.dateSubmitted","value":"2017-09-20T16:51:06Z"},{"label":"dcterms.description","value":"Department of Physiology and Biophysics."},{"label":"dcterms.extent","value":"146 pg."},{"label":"dcterms.format","value":"Application/PDF"},{"label":"dcterms.identifier","value":"http://hdl.handle.net/11401/76748"},{"label":"dcterms.issued","value":"2015-05-01"},{"label":"dcterms.language","value":"en_US"},{"label":"dcterms.provenance","value":"Made available in DSpace on 2017-09-20T16:51:06Z (GMT). No. of bitstreams: 1\nYerramilli_grad.sunysb_0771E_12626.pdf: 4127855 bytes, checksum: 5b18917f109d13c39fc48f7058190bc8 (MD5)\n  Previous issue date: 2015"},{"label":"dcterms.publisher","value":"The Graduate School, Stony Brook University: Stony Brook, NY."},{"label":"dcterms.subject","value":"Biophysics"},{"label":"dcterms.title","value":"Interactions between \u00ce\u00b3-Synuclein and Phospholipase C\u00ce\u00b2 and their effects on Cancer Phenotypes"},{"label":"dcterms.type","value":"Dissertation"},{"label":"dc.type","value":"Dissertation"}],"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/2/15%2F61%2F53%2F15615350113862687581269158699095431296/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/2/15%2F61%2F53%2F15615350113862687581269158699095431296","profile":"http://iiif.io/api/image/2/level2.json"}},"on":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/canvas/page-1.json"}]}]}]}