Please use this identifier to cite or link to this item: https://hdl.handle.net/11147/5275
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dc.contributor.authorCan, G.-
dc.contributor.authorAkpınar, B.-
dc.contributor.authorBaran, Yusuf-
dc.contributor.authorZhivotovsky, B.-
dc.contributor.authorOlsson, M.-
dc.date.accessioned2017-04-10T11:56:30Z
dc.date.available2017-04-10T11:56:30Z
dc.date.issued2013-09
dc.identifier.citationCan, G., Akpınar, B., Baran, Y., Zhivotovsky, B., and Olsson, M. (2013). 5-Fluorouracil signaling through a calcium-calmodulin-dependent pathway is required for p53 activation and apoptosis in colon carcinoma cells. Oncogene, 32(38), 4529-4538. doi:10.1038/onc.2012.467en_US
dc.identifier.issn0950-9232
dc.identifier.issn1476-5594-
dc.identifier.issn0950-9232-
dc.identifier.urihttp://doi.org/10.1038/onc.2012.467
dc.identifier.urihttp://hdl.handle.net/11147/5275
dc.description.abstract5-Fluorouracil (5-FU) is an anti-metabolite that is in clinical use for treatment of several cancers. In cells, it is converted into three distinct fluoro-based nucleotide analogs, which interfere with DNA synthesis and repair, leading to genome impairment and, eventually, apoptotic cell death. Current knowledge states that in certain cell types, 5-FU-induced stress is signaling through a p53-dependent induction of tumor necrosis factor-receptor oligomerization required for death-inducing signaling complex formation and caspase-8 activation. Here we establish a role of calcium (Ca 2+) as a messenger for p53 activation in response to 5-FU. Using a combination of pharmacological and genetic approaches, we show that treatment of colon carcinoma cells stimulates entry of extracellular Ca 2+ through long lasting-type plasma membrane channels, which further directs posttranslational phosphorylation of at least three p53 serine residues (S15, S33 and S37) by means of calmodulin (CaM) activity. Obstructing this pathway by the Ca 2+ -chelator BAPTA (1,2-bis(o-aminophenoxy)ethane- N,N,N',N'-tetraacetic acid) or by inhibitors of CaM efficiently reduces 5-FU-induced caspase activities and subsequent cell death. Moreover, ectopic expression of p53 S15A in HCT116 p53 -/- cells confirmed the importance of a Ca 2+ -CaM-p53 axis in 5-FU-induced extrinsic apoptosis. The fact that a widely used therapeutic drug, such as 5-FU, is operating via this pathway could provide new therapeutic intervention points, or specify new combinatorial treatment regimes. © 2013 Macmillan Publishers Limited.en_US
dc.description.sponsorshipSwedish Science Foundation; Swedish and Stockholm Cancer Societies; Swedish Childhood Cancer Foundation; EC-FP-6 (Chemores); EC-FP-7 (APO-SYS)en_US
dc.language.isoenen_US
dc.publisherNature Publishing Groupen_US
dc.relation.ispartofOncogeneen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectFluorouracilen_US
dc.subjectApoptosisen_US
dc.subjectCalciumen_US
dc.subjectCalmodulinen_US
dc.subjectProtein p53en_US
dc.subjectProteinsen_US
dc.title5-Fluorouracil signaling through a calcium-calmodulin-dependent pathway is required for p53 activation and apoptosis in colon carcinoma cellsen_US
dc.typeArticleen_US
dc.authoridTR119193en_US
dc.institutionauthorBaran, Yusuf-
dc.departmentİzmir Institute of Technology. Molecular Biology and Geneticsen_US
dc.identifier.volume32en_US
dc.identifier.issue38en_US
dc.identifier.startpage4529en_US
dc.identifier.endpage4538en_US
dc.identifier.wosWOS:000324831300008en_US
dc.identifier.scopus2-s2.0-84884588215en_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.identifier.doi10.1038/onc.2012.467-
dc.identifier.pmid23108402en_US
dc.relation.doi10.1038/onc.2012.467en_US
dc.coverage.doi10.1038/onc.2012.467en_US
dc.identifier.wosqualityQ1-
dc.identifier.scopusqualityQ1-
item.grantfulltextopen-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.fulltextWith Fulltext-
item.languageiso639-1en-
item.openairetypeArticle-
item.cerifentitytypePublications-
crisitem.author.dept04.03. Department of Molecular Biology and Genetics-
Appears in Collections:Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik
OpenAIRE Collection / OpenAIRE Koleksiyonu
PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection
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