Tumor necrosis factor receptor-associated factor 6 interaction with alpha-synuclein enhances cell death through the Nuclear Factor-kB pathway.
CHIP, carboxyl terminus of Hsp70-interaction protein
EMSA, Electrophoretic Mobility Shift Assay
LB, Lewy bodies
NF-κB, nuclear factor κB
PD, Parkinson's disease
SIAH, seven in absentia homolog
TRAF6 and NF-κB
TRAF6, tumor necrosis factor receptor-associated factor 6
alpha-synuclein
asyn, alpha-synuclein
cell death
cytokines
Journal
IBRO reports
ISSN: 2451-8301
Titre abrégé: IBRO Rep
Pays: England
ID NLM: 101691215
Informations de publication
Date de publication:
Dec 2020
Dec 2020
Historique:
received:
01
07
2020
accepted:
28
08
2020
entrez:
28
9
2020
pubmed:
29
9
2020
medline:
29
9
2020
Statut:
epublish
Résumé
Parkinson's disease (PD) is a neurodegenerative disease characterized by intracellular inclusions named Lewy bodies (LB), and alpha-synuclein (asyn) is the major component of these protein aggregates. The precise physiological and pathological roles of asyn are not fully understood. Nevertheless, asyn present in LB is ubiquitinated but fails to reach the 26S proteasome. The mutation A30 P is related to an aggressive and early-onset form of PD. Tumor necrosis factor receptor-associated factor 6 (TRAF6) is an E3 ubiquitin ligase, and it interacts and ubiquitinates the asyn in atypical chains (lysine K6, K27, K29, and K33). Methods: Here, we investigated the role of TRAF6 interaction with asyn and the involvement of nuclear factor κB (NF-κB), a key transcription factor in pro-inflammatory signaling pathway activation. We demonstrated that TRAF6 binds to both WT and the mutant form A30 P asyn in an SH-SY5Y cell model. Additionally, the interaction between TRAF6 and WT asyn induced an increase in the activation of NF-κB, leading to changes in
Sections du résumé
BACKGROUND
BACKGROUND
Parkinson's disease (PD) is a neurodegenerative disease characterized by intracellular inclusions named Lewy bodies (LB), and alpha-synuclein (asyn) is the major component of these protein aggregates. The precise physiological and pathological roles of asyn are not fully understood. Nevertheless, asyn present in LB is ubiquitinated but fails to reach the 26S proteasome. The mutation A30 P is related to an aggressive and early-onset form of PD. Tumor necrosis factor receptor-associated factor 6 (TRAF6) is an E3 ubiquitin ligase, and it interacts and ubiquitinates the asyn in atypical chains (lysine K6, K27, K29, and K33). Methods: Here, we investigated the role of TRAF6 interaction with asyn and the involvement of nuclear factor κB (NF-κB), a key transcription factor in pro-inflammatory signaling pathway activation.
RESULTS AND CONCLUSION
CONCLUSIONS
We demonstrated that TRAF6 binds to both WT and the mutant form A30 P asyn in an SH-SY5Y cell model. Additionally, the interaction between TRAF6 and WT asyn induced an increase in the activation of NF-κB, leading to changes in
Identifiants
pubmed: 32984640
doi: 10.1016/j.ibror.2020.08.005
pii: S2451-8301(20)30038-8
pmc: PMC7498709
doi:
Types de publication
Journal Article
Langues
eng
Pagination
218-223Informations de copyright
© 2020 The Authors.
Références
J Neurosci Res. 2008 Mar;86(4):845-60
pubmed: 17969100
Nat Cell Biol. 2005 Aug;7(8):758-65
pubmed: 16056267
Nat Genet. 1998 Feb;18(2):106-8
pubmed: 9462735
J Biol Chem. 2011 Jul 15;286(28):25108-17
pubmed: 21454471
Proc Natl Acad Sci U S A. 2013 Oct 29;110(44):17726-31
pubmed: 24043770
Front Immunol. 2018 Aug 09;9:1849
pubmed: 30140268
J Biol Chem. 2006 May 19;281(20):14041-7
pubmed: 16565081
Ann Neurol. 2004 Feb;55(2):164-73
pubmed: 14755719
Expert Opin Ther Targets. 2007 Feb;11(2):123-32
pubmed: 17227229
Cell Death Dis. 2019 Feb 12;10(2):133
pubmed: 30755581
Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7531-6
pubmed: 9207126
J Biol Chem. 2006 Oct 6;281(40):29739-52
pubmed: 16847063
Science. 1997 Jun 27;276(5321):2045-7
pubmed: 9197268
Exp Cell Res. 2000 Jan 10;254(1):14-24
pubmed: 10623461
Proc Natl Acad Sci U S A. 2011 Mar 8;108(10):4194-9
pubmed: 21325059
Brain Behav. 2018 Feb 04;8(3):e00915
pubmed: 29541535
J Cell Sci. 2014 Aug 15;127(Pt 16):3488-504
pubmed: 24928900
Proc Natl Acad Sci U S A. 2004 Apr 13;101(15):5500-5
pubmed: 15064394
Front Neurosci. 2018 Feb 19;12:80
pubmed: 29515354
PLoS Genet. 2014 Nov 13;10(11):e1004741
pubmed: 25393002
J Biol Chem. 2011 Apr 1;286(13):11649-58
pubmed: 21292769
Immunol Rev. 2012 Mar;246(1):95-106
pubmed: 22435549
Neurology. 2009 Jan 13;72(2):110-6
pubmed: 18987353
Cell Mol Neurobiol. 2008 Jan;28(1):21-33
pubmed: 17712623
Nature. 1997 Aug 28;388(6645):839-40
pubmed: 9278044
Trends Biochem Sci. 2000 Nov;25(11):524-7
pubmed: 11084358
Proc Natl Acad Sci U S A. 2007 Nov 20;104(47):18754-9
pubmed: 18000063
Hum Mol Genet. 2010 Oct 1;19(19):3759-70
pubmed: 20634198
Adv Exp Med Biol. 1996;389:261-9
pubmed: 8861020
Nat Med. 2001 Oct;7(10):1144-50
pubmed: 11590439
Toxicol Mech Methods. 2011 Jul;21(6):435-43
pubmed: 21417633
J Neuroinflammation. 2016 Nov 24;13(1):297
pubmed: 27881137
Oncogene. 2001 Oct 1;20(44):6482-91
pubmed: 11607847
Cold Spring Harb Perspect Biol. 2009 Dec;1(6):a001651
pubmed: 20457564
Nat Med. 2004 Jul;10 Suppl:S10-7
pubmed: 15272267
J Biol Chem. 2005 Jun 24;280(25):23727-34
pubmed: 15845543
Signal Transduct Target Ther. 2017;2:
pubmed: 29158945