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dc.contributor.authorLu, Xue
dc.contributor.authorAlam, Umber
dc.contributor.authorWillis, Charlene
dc.contributor.authorKennedy, Derek
dc.date.accessioned2021-05-28T03:37:32Z
dc.date.available2021-05-28T03:37:32Z
dc.date.issued2021
dc.identifier.issn0188-4409
dc.identifier.doi10.1016/j.arcmed.2020.10.002
dc.identifier.urihttp://hdl.handle.net/10072/404735
dc.description.abstractBACKGROUND: Ras-GTPase activating protein SH3-domain-binding proteins (G3BP) are a small family of RNA-binding proteins implicated in regulating gene expression. Changes in expression of G3BPs are correlated to several cancers including thyroid, colon, pancreatic and breast cancer. G3BPs are important regulators of stress granule (SG) formation and function. SG are ribonucleoprotein (RNP) particles that respond to cellular stresses to triage mRNA resulting in transcripts being selectively degraded, stored or translated resulting in a change of gene expression which confers a survival response to the cell. These changes in gene expression contribute to the development of drug resistance. Many RNA viruses, including Chikungunya (and potentially Coronavirus), dismantle SG so that the cell cannot respond to the viral infection. Non-structural protein 3 (nsP3), from the Chikungunya virus, has been shown to translocate G3BP away from SG. Interestingly in cancer cells, the formation of SG is correlated to drug-resistance and blocking SG formation has been shown to reestablish the efficacy of the anticancer drug bortezomib. METHODS: Chikungunya nsP3 was transfected into breast cancer cell lines T47D and MCF7 to disrupt SG formation. Changes in the cytotoxicity of bortezomib were measured. RESULTS: Bortezomib cytotoxicity in breast cancer cell lines changed with a 22 fold decrease in its IC50 for T47D and a 7 fold decrease for MCF7 cells. CONCLUSIONS: Chikungunya nsP3 disrupts SG formation. As a result, it increases the cytotoxicity of the FDA approved drug, bortezomib. In addition, the increased cytotoxicity appears to correlate to improved bortezomib selectivity when compared to control cell lines.
dc.description.peerreviewedYes
dc.languageEnglish
dc.publisherElsevier
dc.relation.ispartofpagefrom48
dc.relation.ispartofpageto57
dc.relation.ispartofissue1
dc.relation.ispartofjournalArchives of Medical Research
dc.relation.ispartofvolume52
dc.subject.fieldofresearchMedical and Health Sciences
dc.subject.fieldofresearchcode11
dc.subject.keywordsScience & Technology
dc.subject.keywordsLife Sciences & Biomedicine
dc.subject.keywordsMedicine, Research & Experimental
dc.subject.keywordsResearch & Experimental Medicine
dc.subject.keywordsG3BP
dc.titleRole of Chikungunya nsP3 in Regulating G3BP1 Activity, Stress Granule Formation and Drug Efficacy
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationLu, X; Alam, U; Willis, C; Kennedy, D, Role of Chikungunya nsP3 in Regulating G3BP1 Activity, Stress Granule Formation and Drug Efficacy, Archives of Medical Research, 2021, 52 (1), pp. 48-57
dcterms.dateAccepted2020-10-01
dc.date.updated2021-05-28T03:36:36Z
gro.hasfulltextNo Full Text
gro.griffith.authorWillis, Charlene
gro.griffith.authorLu, Xue
gro.griffith.authorAlam, Umber


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