Please use this identifier to cite or link to this item: http://hdl.handle.net/11452/34162
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dc.contributor.authorYerlikaya, Azmi-
dc.contributor.authorOkur, Emrah-
dc.contributor.authorBaykal, Ahmet Tarik-
dc.contributor.authorAcilan, Ceyda-
dc.contributor.authorBoyaci, Ihsan-
dc.date.accessioned2023-09-29T10:11:11Z-
dc.date.available2023-09-29T10:11:11Z-
dc.date.issued2015-01-15-
dc.identifier.citationYerlikaya, A. vd. (2015). "A proteomic analysis of p53-independent induction of apoptosis by bortezomib in 4T1 breast cancer cell line". Journal of Proteomics, 113, 315-325.en_US
dc.identifier.issn1874-3919-
dc.identifier.urihttps://doi.org/10.1016/j.jprot.2014.09.010-
dc.identifier.urihttps://www.sciencedirect.com/science/article/pii/S1874391914004266-
dc.identifier.urihttp://hdl.handle.net/11452/34162-
dc.description.abstractThe 26S proteasome is a proteolytic enzyme found in both cytoplasm and nucleus. In this study, we examined the differential expression of proteasome inhibitor bortezomib-induced proteins in p53-deficient 4T1 cells. It was found that GRP78 and TCEB2 were over-expressed in response to treatment with bortezomib for 24 h. Next, we analyzed the expression of intracellular proteins in response to treatment with 100 nM bortezomib for 24 h by label-free LC-MS/MS. These analyses showed that Hsp70, the 26S proteasome non-ATPase regulatory subunit 14 and sequestosome 1 were increased at least 2 fold in p53-deficient 4T1 cells. The proteins identified by label-free LC-MS/MS were then analyzed by Ingenuity Pathway Analysis (IPA) Tool to determine biological networks affected by inhibition of the 26S proteasome. The analysis results showed that post-translational modifications, protein folding, DNA replication, energy production and nucleic acid metabolism were found to be among the top functions affected by the 26S proteasome inhibition. The biological network analysis indicated that ubiquitin may be the central regulator of the pathways modulated after bortezomib-treatment. Further investigation of the mechanism of the proteins modulated in response to the proteasomal inhibition may lead to the design of more effective and novel therapeutic strategies for cancer. Biological significance Although the proteasome inhibitor bortezomib is approved and used for the treatment of human cancer (multiple myeloma), the mechanism of action is not entirely understood. A number of studies showed that proteasome inhibitors induced apoptosis through upregulation of tumor suppressor protein p53. However, the role of tumor suppressor protein p53 in bortezomib-induced apoptosis is controversial and not well-understood. The tumor suppressor p53 is mutated in at least 50% of human cancers and is strongly induced by proteasomal inhibition. Some also reported that the proteasome inhibitor can induce apoptosis in a p53-independent manner. Also, it is reported that Noxa, a target of p53, is induced in response to proteasomal inhibition in a p53-independent manner. However, we have also previously reported that neither Puma nor Noxa are induced by proteasomal inhibition in p53-null 4T1 breast cancer cells, which is commonly used for in vivo breast cancer tumor models. The current results provided additional targets of proteasome inhibitor bortezomib and may therefore help in understanding the p53-independent mechanism of apoptosis induction by proteasome inhibitors. In addition, the results presented in this current study report for the first time that proteasomal subunit Psmd14, anti-apoptotic GRP78, anti apoptotic protein Card10, Dffb, Traf3 and Trp53bp2 are regulated and overexpressed in response to proteasome inhibitor bortezomib in p53-deficient 4T1 cells. Therefore, novel therapeutic strategies targeting these anti-apoptotic or pro-apoptotic proteins as well as inhibiting the proteasome simultaneously may be more effective against cancer cells. The proteins identified here present new avenues for the development of anti-cancer drugs.en_US
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.rightsAtıf Gayri Ticari Türetilemez 4.0 Uluslararasıtr_TR
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectBiochemistry & Molecular biologyen_US
dc.subjectApoptosisen_US
dc.subjectBortezomiben_US
dc.subjectCanceren_US
dc.subjectProteasomeen_US
dc.subjectProteomicsen_US
dc.subjectUbiquitinen_US
dc.subjectUbiquitin-proteasome pathwayen_US
dc.subjectIn-vitroen_US
dc.subjectInhibitor bortezomiben_US
dc.subjectProtein-degradationen_US
dc.subjectKappa-Ben_US
dc.subjectSensitivityen_US
dc.subjectDeathen_US
dc.subjectDecarboxylaseen_US
dc.subjectP53en_US
dc.subject.meshAntineoplastic agentsen_US
dc.subject.meshApoptosisen_US
dc.subject.meshBoronic acidsen_US
dc.subject.meshBreast neoplasmsen_US
dc.subject.meshCell line, tumoren_US
dc.subject.meshDNA replicationen_US
dc.subject.meshDNA, neoplasmen_US
dc.subject.meshEnergy metabolismen_US
dc.subject.meshFemaleen_US
dc.subject.meshHumansen_US
dc.subject.meshProteasome endopeptidase complexen_US
dc.subject.meshProtein foldingen_US
dc.subject.meshProtein processing, post-translationalen_US
dc.subject.meshProteomeen_US
dc.subject.meshProteomicsen_US
dc.subject.meshPyrazinesen_US
dc.subject.meshTumor suppressor protein p53en_US
dc.titleA proteomic analysis of p53-independent induction of apoptosis by bortezomib in 4T1 breast cancer cell lineen_US
dc.typeArticleen_US
dc.identifier.wos000347582200022tr_TR
dc.identifier.scopus2-s2.0-84938493066tr_TR
dc.relation.tubitakSBAG 109S035tr_TR
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergitr_TR
dc.contributor.departmentUludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyokimya Anabilim Dalı.tr_TR
dc.contributor.orcid0000-0003-4875-5472tr_TR
dc.identifier.startpage315tr_TR
dc.identifier.endpage325tr_TR
dc.identifier.volume113tr_TR
dc.relation.journalJournal of Proteomicsen_US
dc.contributor.buuauthorUlukaya, Engin-
dc.contributor.researcheridK-5792-2018tr_TR
dc.relation.collaborationYurt içitr_TR
dc.identifier.pubmed25305590tr_TR
dc.subject.wosBiochemical research methodsen_US
dc.indexed.wosSCIEen_US
dc.indexed.scopusScopusen_US
dc.indexed.pubmedPubMeden_US
dc.wos.quartileQ1en_US
dc.contributor.scopusid6602927353tr_TR
dc.subject.scopusProteasome inhibitors; Proteasome endopeptidase complex; Bortezomiben_US
dc.subject.emtreeBortezomiben_US
dc.subject.emtreeCard10 proteinen_US
dc.subject.emtreeCaspase activated deoxyribonucleaseen_US
dc.subject.emtreeCell proteinen_US
dc.subject.emtreeGlucose regulated protein 78en_US
dc.subject.emtreeNon atpase ase regulatory subunit 14en_US
dc.subject.emtreeProteasomeen_US
dc.subject.emtreeProtein p53en_US
dc.subject.emtreeSequestosome 1en_US
dc.subject.emtreeTceb2 proteinen_US
dc.subject.emtreeTrp53bp2 proteinen_US
dc.subject.emtreeTumor necrosis factor receptor associated factor 3en_US
dc.subject.emtreeUbiquitinen_US
dc.subject.emtreeUnclassified drugen_US
dc.subject.emtreeAntineoplastic agenten_US
dc.subject.emtreeATP dependent 26S proteaseen_US
dc.subject.emtreeBoronic acid derivativeen_US
dc.subject.emtreeBortezomiben_US
dc.subject.emtreeDNAen_US
dc.subject.emtreeProteasomeen_US
dc.subject.emtreeProtein p53en_US
dc.subject.emtreeProteomeen_US
dc.subject.emtreePyrazine derivativeen_US
dc.subject.emtreeTP53 proteinen_US
dc.subject.emtreeHumanen_US
dc.subject.emtreeApoptosisen_US
dc.subject.emtreeArticleen_US
dc.subject.emtreeBreast canceren_US
dc.subject.emtreeBreast cancer cell lineen_US
dc.subject.emtreeControlled studyen_US
dc.subject.emtreeDNA replicationen_US
dc.subject.emtreeEnergy yielden_US
dc.subject.emtreeLiquid chromatographyen_US
dc.subject.emtreeNucleic acid metabolismen_US
dc.subject.emtreePriority journalen_US
dc.subject.emtreeProtein expressionen_US
dc.subject.emtreeProtein foldingen_US
dc.subject.emtreeProtein processingen_US
dc.subject.emtreeProteomicsen_US
dc.subject.emtreeTandem mass spectrometryen_US
dc.subject.emtreeBiosynthesisen_US
dc.subject.emtreeBreast neoplasmsen_US
dc.subject.emtreeDrug effectsen_US
dc.subject.emtreeEnergy metabolismen_US
dc.subject.emtreeFemaleen_US
dc.subject.emtreeHumanen_US
dc.subject.emtreeMetabolismen_US
dc.subject.emtreePathologyen_US
dc.subject.emtreeTumor cell lineen_US
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