| Autor: |
Della C, David, Robert, Layfield, Louise, Serpell, Yolanda, Narain, Michel, Goedert, Maria Grazia, Spillantini |
| Rok vydání: |
2002 |
| Předmět: |
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| Zdroj: |
Journal of neurochemistry. 83(1) |
| ISSN: |
0022-3042 |
| 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 |
| Externí odkaz: |
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