David, Della C, Layfield, Robert, Serpell, Louise, Narain, Yolanda, Goeder, Michel and Spillantini, Maria Grazia (2002) Proteasomal degradation of tau protein. Journal of Neurochemistry, 83 (1). pp. 176-185. ISSN 0022-3042

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Abstract

Filamentous inclusions composed of the microtubule-associated protein tau are a defining characteristic of a large number of neurodegenerative diseases. Here we show that tau degradation in stably transfected and non-transfected SH-SY5Y cells is blocked by the irreversible proteasome inhibitor lactacystin. Further, we find that in vitro, natively unfolded tau can be directly processed by the 20S proteasome without a requirement for ubiquitylation, and that a highly reproducible pattern of degradation intermediates is readily detectable during this process. Analysis of these intermediates shows that 20S proteasomal processing of tau is bi-directional, proceeding from both N- and C-termini, and that populations of relatively stable intermediates arise probably because of less efficient digestion of the C-terminal repeat region. Our results are consistent with an in vivo role for the proteasome in tau degradation and support the existence of ubiquitin-independent pathways for the proteasomal degradation of unfolded proteins.

Item Type:	Article
Schools and Departments:	School of Life Sciences > Biochemistry
Depositing User:	Louise Serpell
Date Deposited:	06 Feb 2012 21:27
Last Modified:	26 Mar 2012 12:47
URI:	http://sro.sussex.ac.uk/id/eprint/31295

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