dc.contributor.advisor	Fésüs, László
dc.contributor.author	Ergülen, Elvan
dc.contributor.department	Molekuláris sejt- és immunbiológia doktori iskola	hu
dc.contributor.submitterdep	DE--Általános Orvostudományi Kar -- Biokémiai és Molekuláris Biológiai Intézet
dc.date.accessioned	2016-10-18T16:27:26Z
dc.date.available	2016-10-18T16:27:26Z
dc.date.defended	2016-10-26
dc.date.issued	2016
dc.description.abstract	Transglutaminase 2 (TG2) is a multifunctional enzyme which participates in posttranslational modification of proteins, such as catalyzing calcium dependent crosslinking of proteins, incorporation of primary amines and deamidation of proteins. In addition, TG2 also acts as a G protein, has protein disulphide isomerase, protein kinase activities and plays non-enzymatic roles such as functioning as an adaptor protein, cell surface adhesion mediator and forming protein scaffolds. In our study, we first compared the transamidation activity and calcium sensitivities of Gly224 and Val224 variants of TG2 and found that the Val variant, which is the actual wild type variant in the human genome, exhibits significantly higher activity and calcium sensitivity compared to Gly variant which was used in many previous studies in other laboratories. In the rest of the project we used Val224 “wild type” variant of TG2. Our main aim in this study was to identify the novel interacting partners of human TG2. For this aim, we used NB4 promyelocytic leukemia (APL) cell line which overexpresses TG2 and also other APL related genes upon differentiation by ATRA. Among several other interacting partners, we identified DNAJA1 as a novel interacting partner of TG2. We further comfirmed this interaction via several in vitro experiments such as ELISA and SPR measurements. The same experiments were performed to determine the DNAJA1 binding domain of TG2 and results suggested that core domain of TG2 is the essential domain for TG2-DNAJA1 interaction. Furthermore, DNAJA1 was found to interact mainly with open conformer of TG2. To explore the effect of DNAJA1 on crosslinking activity of TG2 we carried out some in vitro and in situ experiments and observed that DNAJA1 inversely regulates the activity of TG2. Moreover, DNAJA1 was also identified as a novel substrate of TG2. DNAJA1 and TG2 have been independently reported to regulate similar cellular and pathological processes, such as cellular transport, apoptosis, neurodegenerative disorders and cancer. We propose that both the proteins regulate these overlapping functions via intermolecular interactions.	hu_HU
dc.description.corrector	de
dc.format.extent	65	hu_HU
dc.identifier.uri	http://hdl.handle.net/2437/231112
dc.language.iso	en	hu_HU
dc.subject	Transglutaminase 2	hu_HU
dc.subject	transamidation
dc.subject	DNAJA1/HSP40
dc.subject	core domain
dc.subject	protein-protein interaction
dc.subject	in situ crosslinking activity
dc.subject	GST pull down assay
dc.subject	surface plasmon resonance
dc.subject.discipline	Elméleti orvostudományok	hu
dc.subject.sciencefield	Orvostudományok	hu
dc.title	DNAJA1 as a novel interacting partner of transglutaminase 2	hu_HU
dc.title.translated	DNAJA1 as a novel interacting partner of transglutaminase 2	hu_HU
dc.type	PhD, doktori értekezés	hu

DNAJA1 as a novel interacting partner of transglutaminase 2

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