PMID- 38142771
OWN - NLM
STAT- MEDLINE
DCOM- 20240122
LR  - 20240202
IS  - 1878-5875 (Electronic)
IS  - 1357-2725 (Linking)
VI  - 167
DP  - 2024 Feb
TI  - Molecular and cellular evidence of a direct interaction between the TRAF2 
      C-terminal domain and ganglioside GM1.
PG  - 106508
LID - S1357-2725(23)00147-4 [pii]
LID - 10.1016/j.biocel.2023.106508 [doi]
AB  - TNF receptor-associated factor 2 (TRAF2) is involved in different cellular 
      processes including signal transduction and transcription regulation. We here 
      provide evidence of a direct interaction between the TRAF domain of TRAF2 and the 
      monosialotetrahexosylganglioside (GM1). Previously, we showed that the TRAF 
      domain occurs mainly in a trimeric form in solution, but it can also exist as a 
      stable monomer when in the nanomolar concentration range. Here, we report that 
      the quaternary structure of the TRAF domain is also affected by pH changes, since 
      a weakly acidic pH (5.5) favors the dissociation of the trimeric TRAF domain into 
      stable monomers, as previously observed at neutral pH (7.6) with the diluted 
      protein. The TRAF domain-GM1 binding was similar at pH 5.5 and 7.6, suggesting 
      that GM1 interacts with both the trimeric and monomeric forms of the protein. 
      However, only the monomeric protein appeared to cause membrane deformation and 
      inward vesiculation in GM1-containing giant unilamellar vesicles (GUVs). The 
      formation of complexes between GM1 and TRAF2, or its TRAF domain, was also 
      observed in cultured human leukemic HAP1 cells expressing either the truncated 
      TRAF domain or the endogenous full length TRAF2. The GM1-protein complexes were 
      observed after treatment with tunicamycin and were more concentrated in cells 
      undergoing apoptosis, a condition which is known to cause cytoplasm 
      acidification. These findings open the avenue for future studies aimed at 
      deciphering the physiopathological relevance of the TRAF domain-GM1 interaction.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.
FAU - De Luca, Anastasia
AU  - De Luca A
AD  - Department of Biology, University of Tor Vergata, Rome, Italy.
FAU - Faienza, Fiorella
AU  - Faienza F
AD  - Department of Chemical Sciences and Technologies, University of Tor Vergata, 
      Rome, Italy.
FAU - Fulci, Chiara
AU  - Fulci C
AD  - Department of Chemical Sciences and Technologies, University of Tor Vergata, 
      Rome, Italy.
FAU - Nicolai, Eleonora
AU  - Nicolai E
AD  - Department of Experimental Medicine, University of Tor Vergata, Rome, Italy.
FAU - Calligari, Paolo
AU  - Calligari P
AD  - Department of Chemical Sciences and Technologies, University of Tor Vergata, 
      Rome, Italy.
FAU - Palumbo, Camilla
AU  - Palumbo C
AD  - Department of Clinical Sciences and Translational Medicine, University of Tor 
      Vergata, Rome, Italy. Electronic address: camilla.palumbo@uniroma2.it.
FAU - Caccuri, Anna Maria
AU  - Caccuri AM
AD  - Department of Chemical Sciences and Technologies, University of Tor Vergata, 
      Rome, Italy; The NAST Centre for Nanoscience and Nanotechnology and Innovative 
      Instrumentation, University of Tor Vergata, Rome, Italy. Electronic address: 
      caccuri@uniroma2.it.
LA  - eng
PT  - Journal Article
DEP - 20231222
PL  - Netherlands
TA  - Int J Biochem Cell Biol
JT  - The international journal of biochemistry & cell biology
JID - 9508482
RN  - 0 (TNF Receptor-Associated Factor 2)
RN  - 37758-47-7 (G(M1) Ganglioside)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - 0 (NF-kappa B)
SB  - IM
MH  - Humans
MH  - TNF Receptor-Associated Factor 2/metabolism
MH  - *G(M1) Ganglioside
MH  - *Signal Transduction
MH  - Ubiquitin-Protein Ligases/metabolism
MH  - Gene Expression Regulation
MH  - NF-kappa B/metabolism
OTO - NOTNLM
OT  - Acidic pH
OT  - GM1
OT  - Giant unilamellar vesicles
OT  - TRAF domain
OT  - TRAF2
COIS- Declaration of Competing Interest None.
EDAT- 2023/12/25 00:42
MHDA- 2024/01/22 06:43
CRDT- 2023/12/24 19:26
PHST- 2023/07/25 00:00 [received]
PHST- 2023/11/30 00:00 [revised]
PHST- 2023/12/20 00:00 [accepted]
PHST- 2024/01/22 06:43 [medline]
PHST- 2023/12/25 00:42 [pubmed]
PHST- 2023/12/24 19:26 [entrez]
AID - S1357-2725(23)00147-4 [pii]
AID - 10.1016/j.biocel.2023.106508 [doi]
PST - ppublish
SO  - Int J Biochem Cell Biol. 2024 Feb;167:106508. doi: 10.1016/j.biocel.2023.106508. 
      Epub 2023 Dec 22.