Degradation of α-synuclein by proteasome

M. Catherine Bennett, John F. Bishop, Yan Leng, P. Boon Chock, Thomas N. Chase, M Maral Mouradian

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Abstract

Mutations in α-synuclein are known to be associated with Parkinson's disease (PD). The coexistence of this neuronal protein with ubiquitin and proteasome subunits in Lewy bodies in sporadic disease suggests that alterations of α-synuclein catabolism may contribute to the pathogenesis of PD. The degradation pathway of α-synuclein has not been identified nor has the kinetics of this process been described. We investigated the degradation kinetics of both wild-type and A53T mutant 6XHis-tagged α-synuclein in transiently transfected SHSY5Y cells. Degradation of both isoforms followed first-order kinetics over 24 h as monitored by the pulse-chase method. However, the t( 1/2 ) of mutant α-synuclein was 50% longer than that of the wild-type protein (p < 0.01). The degradation of both recombinant proteins and endogenous α-synuclein in these cells was blocked by the selective proteasome inhibitor β-lactone (40 μM), indicating that both wild-type and A53T mutant α-synuclein are degraded by the ubiquitin-proteasome pathway. The slower degradation of mutant α-synuclein provides a kinetic basis for its intracellular accumulation, thus favoring its aggregation.

Original languageEnglish (US)
Pages (from-to)33855-33858
Number of pages4
JournalJournal of Biological Chemistry
Volume274
Issue number48
DOIs
StatePublished - Nov 26 1999

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Synucleins
Proteasome Endopeptidase Complex
Degradation
Kinetics
Ubiquitin
Parkinson Disease
Lewy Bodies
Proteasome Inhibitors
Lactones
Recombinant Proteins
Protein Isoforms
Proteins
Agglomeration
Mutation

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Bennett, M. C., Bishop, J. F., Leng, Y., Chock, P. B., Chase, T. N., & Mouradian, M. M. (1999). Degradation of α-synuclein by proteasome. Journal of Biological Chemistry, 274(48), 33855-33858. https://doi.org/10.1074/jbc.274.48.33855
Bennett, M. Catherine ; Bishop, John F. ; Leng, Yan ; Chock, P. Boon ; Chase, Thomas N. ; Mouradian, M Maral. / Degradation of α-synuclein by proteasome. In: Journal of Biological Chemistry. 1999 ; Vol. 274, No. 48. pp. 33855-33858.
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Bennett, MC, Bishop, JF, Leng, Y, Chock, PB, Chase, TN & Mouradian, MM 1999, 'Degradation of α-synuclein by proteasome', Journal of Biological Chemistry, vol. 274, no. 48, pp. 33855-33858. https://doi.org/10.1074/jbc.274.48.33855

Degradation of α-synuclein by proteasome. / Bennett, M. Catherine; Bishop, John F.; Leng, Yan; Chock, P. Boon; Chase, Thomas N.; Mouradian, M Maral.

In: Journal of Biological Chemistry, Vol. 274, No. 48, 26.11.1999, p. 33855-33858.

Research output: Contribution to journalArticle

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Bennett MC, Bishop JF, Leng Y, Chock PB, Chase TN, Mouradian MM. Degradation of α-synuclein by proteasome. Journal of Biological Chemistry. 1999 Nov 26;274(48):33855-33858. https://doi.org/10.1074/jbc.274.48.33855