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dc.contributor.authorYalçın, Esra
dc.contributor.authorBeker, Mustafa Çağlar
dc.contributor.authorTürkseven, Şeyma
dc.contributor.authorÇağlayan, Berrak
dc.contributor.authorGürel, Büşra
dc.contributor.authorKılıç, Ülkan
dc.contributor.authorÇağlayan, Ahmet Burak
dc.contributor.authorKalkan, Rabia
dc.contributor.authorBaykal, Ahmet Tarık
dc.contributor.authorKeleştemur, Taha
dc.contributor.authorKılıç, Ertuğrul
dc.date.accessioned2019-12-26T07:00:49Z
dc.date.available2019-12-26T07:00:49Z
dc.date.issued2019en_US
dc.identifier.citationYalçın, E., Beker, M. Ç., Türkseven, Ş., Çağlayan, B., Gürel, B., Kılıç, Ü. ... Kılıç, E. (2019). Evidence that melatonin downregulates Nedd4-1 E3 ligase and its role in cellular survival. Toxicology and Applied Pharmacology, 379. https://doi.org/10.1016/j.taap.2019.114686en_US
dc.identifier.issn0041-008X
dc.identifier.issn1096-0333
dc.identifier.urihttps://doi.org/10.1016/j.taap.2019.114686
dc.identifier.urihttps://hdl.handle.net/20.500.12511/4708
dc.description.abstractIndolamine melatonin structurally resembles non-covalent proteasome inhibitors; however, the role of ubiquitin proteasome system (UPS) in neuronal survival and how melatonin carries out UPS inhibition remain largely unknown. With the use of melatonin treated cells, we evaluated the expression of Nedd4-1, an E3 ligase, how melatonin regulates its activity and its relationship with neuronal survival. Nedd4-1 was upregulated in the hypoxic condition in both control and Nedd4-1 overexpressed cells and melatonin treatment reversed its expression in both normoxic and hypoxic conditions, which was associated with increased cellular survival. Melatonin had no effect on the expression of Nedd4-1 at mRNA level. However, when melatonin was administered along with protein synthesis inhibitor cycloheximide, protein level of Nedd4-1 was further reduced, indicating that melatonin possibly downregulates Nedd4-1 after its synthesis. Notably, co-immunoprecipitation analyses followed by Liquid chromatography Mass Spectrometry (LC-MS/MS) revealed that melatonin may dissociate ribosomal proteins, such as RS19, RL23A, and nucleophosmin from Nedd4-1, while 40S ribosomal protein S7 and 60S ribosomal protein L35 came into contact with Nedd4-1 upon melatonin treatment. By using IPA analyses, we obtained further data indicated novel target molecules of melatonin in hypoxic conditions, including OTOF, SF3B2, IPO5, ST13, FGFR3, Mxl/Mx2, playing roles in RNA splicing and trafficking, growth factor and interferon signaling. Here, we described a new insight into the role of melatonin in UPS functioning by proposing a molecular mechanism through which melatonin regulates Nedd4-1.en_US
dc.language.isoengen_US
dc.publisherAcademic Press Inc Elsevier Scienceen_US
dc.rightsinfo:eu-repo/semantics/embargoedAccessen_US
dc.subjectMelatoninen_US
dc.subjectUbiquitin Proteosome Systemen_US
dc.subjectNedd4-1en_US
dc.subjectProteomicen_US
dc.subjectProteasomeen_US
dc.subjectUbiquitinen_US
dc.titleEvidence that melatonin downregulates Nedd4-1 E3 ligase and its role in cellular survivalen_US
dc.typearticleen_US
dc.relation.journalToxicology and Applied Pharmacologyen_US
dc.departmentİstanbul Medipol Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Fizyoloji Ana Bilim Dalıen_US
dc.departmentİstanbul Medipol Üniversitesi, Rektörlük, Rejeneratif ve Restoratif Tıp Araştırmaları Merkezi (REMER)en_US
dc.departmentİstanbul Medipol Üniversitesi, Uluslararası Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Tıbbi Biyoloji Ana Bilim Dalıen_US
dc.departmentİstanbul Medipol Üniversitesi, Uluslararası Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Fizyoloji Ana Bilim Dalıen_US
dc.authorid0000-0002-1064-7989en_US
dc.authorid0000-0002-9476-8488en_US
dc.authorid0000-0002-5072-132Xen_US
dc.authorid0000-0002-6242-3709en_US
dc.authorid0000-0001-6494-8923en_US
dc.identifier.volume379en_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.identifier.doi10.1016/j.taap.2019.114686en_US


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