ATXN3 deubiquitinates polyUb-PARK2

Stable Identifier
Reaction [transition]
Homo sapiens
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Ataxin-3 (ATXN3) deubiquitinates the C-terminus of PARK2 (Parkin) (Winborn et al. 2008, Durcan et al. 2011). This promotes the degradation of PARK2.

An unstable CAG trinucleotide repeat expansion in the ATXN3 gene leads to elongation of the polyglutamine (polyQ) tract within the ATXN3 protein, and is believed to be the cause of Machado-Joseph disease (MJD) or spinocerebellar ataxia type 3 (SCA3), the most common dominantly inherited form of ataxia (Martins et al. 2007). Both wild-type and polyQ-expanded ATXN3 can deubiquitinate PARK2, regardless of the lysine residue used to assemble poly-Ub chains. The polyQ-expanded ATXN3 deubiquitinates PARK2 more efficiently than wild-type ATXN3, but the mutant rather than the wild-type ATXN3 promoted the clearance of PARK2 via the autophagy pathway. This apparent contradiction may be due to increased removal of K27- and K29-linked Ub conjugates on PARK2 by the polyQ-expanded ATXN3; Ub conjugates linked in this manner to PARK2 may protect it from autophagic degradation (Durcan et al. 2011).

Literature References
PubMed ID Title Journal Year
18599482 The deubiquitinating enzyme ataxin-3, a polyglutamine disease protein, edits Lys63 linkages in mixed linkage ubiquitin chains

Winborn, BJ, Travis, SM, Todi, SV, Scaglione, KM, Xu, P, Williams, AJ, Cohen, RE, Peng, J, Paulson, HL

J. Biol. Chem. 2008
20940148 The Machado-Joseph disease-associated mutant form of ataxin-3 regulates parkin ubiquitination and stability

Durcan, TM, Kontogiannea, M, Thorarinsdottir, T, Fallon, L, Williams, AJ, Djarmati, A, Fantaneanu, T, Paulson, HL, Fon, EA

Hum. Mol. Genet. 2011
Participant Of
Catalyst Activity
Catalyst Activity
thiol-dependent ubiquitinyl hydrolase activity of ATXN3:polyUb-PARK2 [cytosol]
Physical Entity
Orthologous Events
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