Degron capability of the hydrophobic C-terminus of the polyglutamine disease protein, ataxin-3.
RRID:AB_1281300
RRID:AB_2307391
RRID:SCR_001010
ataxia
deubiquitinase
isoform
neurodegeneration
polyglutamine
proteasome
ubiquitin
Journal
Journal of neuroscience research
ISSN: 1097-4547
Titre abrégé: J Neurosci Res
Pays: United States
ID NLM: 7600111
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
20
11
2019
revised:
27
05
2020
accepted:
08
06
2020
pubmed:
10
7
2020
medline:
18
9
2021
entrez:
10
7
2020
Statut:
ppublish
Résumé
Ataxin-3 is a deubiquitinase and polyglutamine disease protein whose cellular properties and functions are not entirely understood. Mutations in ataxin-3 cause spinocerebellar ataxia type 3 (SCA3), a neurodegenerative disorder that is a member of the polyglutamine family of diseases. Two major isoforms arise from alternative splicing of ATXN3 and are differently toxic in vivo as a result of faster proteasomal degradation of one isoform compared to the other. The isoforms vary only at their C-termini, suggesting that the hydrophobic C-terminus of the more quickly degraded form of ataxin-3 (here referred to as isoform 2) functions as a degron-that is, a peptide sequence that expedites the degradation of its host protein. We explored this notion in this study and present evidence that: (a) the C-terminus of ataxin-3 isoform 2 signals its degradation in a proteasome-dependent manner, (b) this effect from the C-terminus of isoform 2 does not require the ubiquitination of ataxin-3, and (c) the isolated C-terminus of isoform 2 can enhance the degradation of an unrelated protein. According to our data, the C-terminus of ataxin-3 isoform 2 is a degron, increasing overall understanding of the cellular properties of the SCA3 protein.
Identifiants
pubmed: 32643791
doi: 10.1002/jnr.24684
pmc: PMC8693082
mid: NIHMS1762178
doi:
Substances chimiques
Peptides
0
Repressor Proteins
0
polyglutamine
26700-71-0
ATXN3 protein, human
EC 3.4.19.12
Ataxin-3
EC 3.4.19.12
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2096-2108Subventions
Organisme : NINDS NIH HHS
ID : R01 NS086778
Pays : United States
Informations de copyright
© 2020 Wiley Periodicals LLC.
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