TRAF3 can interact with GMEB1 and modulate its anti-apoptotic function

Kotsaris, G.; Kerselidou, Despoina; Koutsoubaris, D.; Constantinou, E.; Malamas, G.; Garyfallos, D. A.; Hatzivassiliou, E. G.

doi:10.1186/s40709-020-00117-2

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TRAF3 can interact with GMEB1 and modulate its anti-apoptotic function

Kotsaris, G.; Kerselidou, Despoina; Koutsoubaris, D. et al.

2020 • In Journal of Biological Research, 27 (1)

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10.1186/s40709-020-00117-2

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Keywords :

Apoptosis; GMEB1; Protein-protein interaction; Signal transduction; TNF; TRAF3

Abstract :

[en] Background: Members of Tumor Necrosis Factor (TNF) Receptor-Associated Factors (TRAFs) family interact with the cytoplasmic tails of TNF receptor family members to mediate signal transduction processes. TRAF3 has a major immunomodulatory function and TRAF3 deficiency has been linked to malignancies, such as multiple myeloma and lymphoid defects. In order to characterize the molecular mechanisms of TRAF3 signaling, the yeast two-hybrid system was used to identify proteins that interact with TRAF3. Results: The yeast two-hybrid screen of a human B cell cDNA library with TRAF3 as bait, identified Glucocorticoid Modulatory Element-Binding Protein 1 (GMEB1) as a TRAF3-interacting protein. Previous studies indicated that GMEB1 functions as a potent inhibitor of caspase activation and apoptosis. The interaction of TRAF3 and GMEB1 proteins was confirmed in mammalian cells lines, using immunoprecipitation assays. The RING and TRAF-C domains of TRAF3 were not essential for this interaction. The overexpression of TRAF3 protein enhanced the anti-apoptotic function of GMEB1 in HeLa cells. On the other hand, downregulation of TRAF3 by RNA interference decreased significantly the ability of GMEB1 to inhibit apoptosis. In addition, LMP1(1-231), a truncated form of the EBV oncoprotein LMP1, that can interact and oligomerize with TRAF3, was also able to cooperate with GMEB1, in order to inhibit apoptosis. Conclusions: Our protein-interaction experiments demonstrated that TRAF3 can interact with GMEB1, which is an inhibitor of apoptosis. In addition, cell viability assays showed that overexpression of TRAF3 enhanced the anti-apoptotic activity of GMEB1, supporting a regulatory role of TRAF3 in GMEB1-mediated inhibition of apoptosis. Better understanding of the molecular mechanism of TRAF3 function will improve diagnostics and targeted therapeutic approaches for TRAF3-associated disorders. © 2020 The Author(s).

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Kotsaris, G.; Department of Genetics, Development and Molecular Biology, School of Biology, Aristotle University of Thessaloniki, University Campus, Thessaloniki, Macedonia, 54124, Greece, Institute for Chemistry and Biochemistry, Freie Universität Berlin, Thielallee 63, Berlin, 14195, Germany

Kerselidou, Despoina ; Université de Liège - ULiège

Koutsoubaris, D.; Department of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, University Campus, Thessaloniki, 54124, Greece

Constantinou, E.; Department of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, University Campus, Thessaloniki, 54124, Greece

Malamas, G.; Department of Genetics, Development and Molecular Biology, School of Biology, Aristotle University of Thessaloniki, University Campus, Thessaloniki, Macedonia, 54124, Greece

Garyfallos, D. A.; Department of Genetics, Development and Molecular Biology, School of Biology, Aristotle University of Thessaloniki, University Campus, Thessaloniki, Macedonia, 54124, Greece, Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, United Kingdom

Hatzivassiliou, E. G.; Department of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, University Campus, Thessaloniki, 54124, Greece

Language :

English

Title :

TRAF3 can interact with GMEB1 and modulate its anti-apoptotic function

Publication date :

2020

Journal title :

Journal of Biological Research

ISSN :

1790-045X

eISSN :

2241-5793

Publisher :

BioMed Central, United Kingdom

Volume :

Issue :

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

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