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Degron capability of the hydrophobic C-terminus of the polyglutamine disease protein, ataxin-3.
J Neurosci Res. 2020 Jul 09 [Online ahead of print]JN

Abstract

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.

Authors+Show Affiliations

Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI, USA.Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI, USA.Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI, USA.Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI, USA. Department of Neurology, Wayne State University School of Medicine, Detroit, MI, USA.Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32643791

Citation

Blount, Jessica R., et al. "Degron Capability of the Hydrophobic C-terminus of the Polyglutamine Disease Protein, Ataxin-3." Journal of Neuroscience Research, 2020.
Blount JR, Johnson SL, Libohova K, et al. Degron capability of the hydrophobic C-terminus of the polyglutamine disease protein, ataxin-3. J Neurosci Res. 2020.
Blount, J. R., Johnson, S. L., Libohova, K., Todi, S. V., & Tsou, W. L. (2020). Degron capability of the hydrophobic C-terminus of the polyglutamine disease protein, ataxin-3. Journal of Neuroscience Research. https://doi.org/10.1002/jnr.24684
Blount JR, et al. Degron Capability of the Hydrophobic C-terminus of the Polyglutamine Disease Protein, Ataxin-3. J Neurosci Res. 2020 Jul 9; PubMed PMID: 32643791.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Degron capability of the hydrophobic C-terminus of the polyglutamine disease protein, ataxin-3. AU - Blount,Jessica R, AU - Johnson,Sean L, AU - Libohova,Kozeta, AU - Todi,Sokol V, AU - Tsou,Wei-Ling, Y1 - 2020/07/09/ PY - 2019/11/20/received PY - 2020/05/27/revised PY - 2020/06/08/accepted PY - 2020/7/10/entrez KW - RRID:AB_1281300 KW - RRID:AB_2307391 KW - RRID:SCR_001010 KW - ataxia KW - deubiquitinase KW - isoform KW - neurodegeneration KW - polyglutamine KW - proteasome KW - ubiquitin JF - Journal of neuroscience research JO - J. Neurosci. Res. N2 - 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. SN - 1097-4547 UR - https://www.unboundmedicine.com/medline/citation/32643791/Degron_capability_of_the_hydrophobic_C-terminus_of_the_polyglutamine_disease_protein,_ataxin-3 L2 - https://doi.org/10.1002/jnr.24684 DB - PRIME DP - Unbound Medicine ER -
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