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dc.contributor.advisorGoldfinger, Lawrence
dc.creatorGaisford, Esme Ann
dc.date.accessioned2020-11-04T15:19:44Z
dc.date.available2020-11-04T15:19:44Z
dc.date.issued2015
dc.identifier.other920555243
dc.identifier.urihttp://hdl.handle.net/20.500.12613/2890
dc.description.abstractThe Ras superfamily consists of over 150 members including the well-known: H-Ras, K-Ras and N-Ras. We propose to target Ras related proliferation in cancer cells by inhibiting Rab vesicle formation. H-Ras, K-Ras and N-Ras are carcinogenic; activating mutations in Ras signaling are generally associated with increased proliferation and survival in cancer cells. Ras is mutated in up to 30% of all human cancers and represents an early survival mutation in cancer cells. Vesicle-bound Ras is trafficked to the plasma membrane, which facilitates interaction between Raf, and effector proteins. Previously, farnsesylation inhibitors, (FTIs) and GTP binding agonists of Ras have been tested as potential pharmacological inhibitors of Ras signaling. However, both drug types have proven ineffective in-vivo. Therefore, there are currently no effective pharmacological treatments to target Ras signaling. However, unpublished data from our lab has identified co-localization of Ras and Rab proteins, in vesicles. Rab proteins are associated with vesicle budding, and endosome development. Rab activity is driven by GTP binding and geranylgeranylation. Non-geranylgeranylated Rab is cytosolic, and does not facilitate endosome formation or vesicle trafficking. We propose that by targeting the Rab specific geranylgeranylation via Rab-specific geranylgeranyl transferase II, we will inhibit Ras associated proliferation. We will pursue this hypothesis by testing three objectives. First, we will produce and test Rab-geranylgeranyl transferase (RGGT)-shRNA to target Rab specific geranylgeranyl transferase. Second, we will illustrate the effect of RGGT knockdown on a downstream signaling target of Ras, specifically pERK levels. Finally, we will measure the direct effect of RGGT knockdown on Ras mediated cellular proliferation. Our results conclude that RGGT-shRNA is a potential target of Ras mediated tumor proliferation.
dc.format.extent60 pages
dc.language.isoeng
dc.publisherTemple University. Libraries
dc.relation.ispartofTheses and Dissertations
dc.rightsIN COPYRIGHT- This Rights Statement can be used for an Item that is in copyright. Using this statement implies that the organization making this Item available has determined that the Item is in copyright and either is the rights-holder, has obtained permission from the rights-holder(s) to make their Work(s) available, or makes the Item available under an exception or limitation to copyright (including Fair Use) that entitles it to make the Item available.
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/
dc.subjectBiology
dc.subjectBiochemistry
dc.subjectCellular Biology
dc.subjectCancer
dc.subjectRab
dc.subjectRas
dc.subjectTrafficking
dc.titleRab-Vesicle Trafficking is Required for Ras-Mediated Proliferation
dc.typeText
dc.type.genreThesis/Dissertation
dc.contributor.committeememberThomas, Gareth
dc.contributor.committeememberHaines, Dale
dc.contributor.committeememberSirover, Michael A.
dc.description.departmentBiomedical Sciences
dc.relation.doihttp://dx.doi.org/10.34944/dspace/2872
dc.ada.noteFor Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu
dc.description.degreeM.S.
refterms.dateFOA2020-11-04T15:19:44Z


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