ATXN3: a multifunctional protein involved in the polyglutamine disease spinocerebellar ataxia type 3.

Publisher: Published by Cambridge University Press in association with the Clinical and Biomedical Computing Unit of the University of Cambridge School of Clinical Medicine Country of Publication: England NLM ID: 100939725 Publication Model: Electronic Cited Medium: Internet ISSN: 1462-3994 (Electronic) Linking ISSN: 14623994 NLM ISO Abbreviation: Expert Rev Mol Med Subsets: MEDLINE

Original Publication: Cambridge, UK : Published by Cambridge University Press in association with the Clinical and Biomedical Computing Unit of the University of Cambridge School of Clinical Medicine, [1997?-

Ataxin-3*/metabolism ; Ataxin-3*/genetics ; Machado-Joseph Disease*/metabolism ; Machado-Joseph Disease*/genetics ; Machado-Joseph Disease*/pathology ; Peptides*/metabolism ; Peptides*/genetics; Humans ; Animals ; DNA Repair ; Gene Expression Regulation ; Proteostasis ; Repressor Proteins/metabolism ; Repressor Proteins/genetics ; Trinucleotide Repeat Expansion

ATXN3 is a ubiquitin hydrolase (or deubiquitinase, DUB), product of the ATXN3 gene, ubiquitously expressed in various cell types including peripheral and neuronal tissues and involved in several cellular pathways. Importantly, the expansion of the CAG trinucleotides within the ATXN3 gene leads to an expanded polyglutamine domain in the encoded protein, which has been associated with the onset of the spinocerebellar ataxia type 3, also known as Machado-Joseph disease, the most common dominantly inherited ataxia worldwide. ATXN3 has therefore been under intensive investigation for decades. In this review, we summarize the main functions of ATXN3 in proteostasis, DNA repair and transcriptional regulation, as well as the emerging role in regulating chromatin structure. The mentioned molecular functions of ATXN3 are also reviewed in the context of the pathological expanded form of ATXN3.

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TESIS2019010003 Agencia Canaria de Investigación, Innovación y Sociedad de la Información

Keywords: ATXN3; DNA damage response; chromatin organization; neurodegeneration; polyglutamine neurodegenerative disorders; proteostasis; spinocerebellar ataxia type-3; ubiquitin hydrolase; ubiquitin proteasome system

EC 3.4.19.12 (Ataxin-3)
26700-71-0 (polyglutamine)
0 (Peptides)
EC 3.4.19.12 (ATXN3 protein, human)
0 (Repressor Proteins)

Date Created: 20240925 Date Completed: 20240925 Latest Revision: 20241003

20241003

PMC11440613

10.1017/erm.2024.10

39320846