Proteasomal degradation of tau protein

Autor: Louise C. Serpell, Yolanda Narain, Robert Layfield, Della C. David, Michel Goedert, Maria Grazia Spillantini
Rok vydání: 2002
Předmět:
Zdroj: Journal of Neurochemistry. 83:176-185
ISSN: 1471-4159
0022-3042
DOI: 10.1046/j.1471-4159.2002.01137.x
Popis: 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.
Databáze: OpenAIRE
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