Abstract
AbstractFilamentous 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.
References
56
Referenced
258
10.1074/jbc.272.3.1791
10.1016/0006-8993(91)90681-K
10.1016/S0300-9084(01)01244-5
10.1126/science.292.5521.1552
10.1042/bj3460155
10.1523/JNEUROSCI.18-18-07061.1998
10.1074/jbc.271.51.32789
10.1146/annurev.bi.65.070196.004101
10.1016/S0300-9084(01)01250-0
10.1074/jbc.272.1.182
10.1126/science.290.5493.985
10.1016/S0006-291X(84)80190-4
10.1016/0166-2236(93)90078-Z
10.1002/j.1460-2075.1990.tb07870.x
10.1016/S0896-6273(00)80615-7
10.1038/383550a0
10.1016/0896-6273(89)90210-9
10.1046/j.1365-2990.2001.00321.x
10.1038/386463a0
10.1016/S0304-3940(99)00476-0
10.1074/jbc.272.45.28218
10.1074/jbc.270.19.11623
10.1046/j.1471-4159.1997.68010430.x
10.1046/j.1471-4159.2000.0750436.x
10.1046/j.1471-4159.1997.69052026.x
10.1074/jbc.273.4.1982
10.1074/jbc.274.6.3363
10.1074/jbc.M112360200
10.1046/j.1365-2990.2001.00335.x
10.1146/annurev.neuro.24.1.1121
10.1038/26652
10.1016/0896-6273(93)90063-W
10.1038/360597a0
10.1016/S1097-2765(01)00407-5
10.1002/j.1460-2075.1993.tb05665.x
10.1046/j.0014-2956.2001.02465.x
10.1006/bbrc.1994.1759
10.1128/MCB.19.5.3664
10.1021/bi00497a001
10.1016/S0092-8674(94)90482-0
10.1046/j.1471-4159.1996.67031183.x
10.1016/S0968-0004(00)01681-9
10.1073/pnas.071043698
10.1038/12647
10.1016/S0021-9258(19)51080-8
/ J. Biol. Chem. / Structural studies of tau protein and Alzheimer paired helical filaments show no evidence for β‐structure by Schweers O. (1994)10.1038/77060
10.1074/jbc.M001555200
10.1093/emboj/19.1.94
10.1016/S0014-5793(01)03115-5
10.1093/emboj/20.10.2367
10.1126/science.289.5487.2117
10.1146/annurev.biochem.68.1.1015
10.1021/bi9724265
10.1111/j.1432-1033.1995.009_1.x
10.1016/S0962-8924(01)02030-X
10.1046/j.1471-4159.1999.0720741.x
Dates
Type | When |
---|---|
Created | 22 years, 5 months ago (March 12, 2003, 2:02 a.m.) |
Deposited | 1 year, 10 months ago (Oct. 17, 2023, 12:20 p.m.) |
Indexed | 1 month ago (July 24, 2025, 6:54 a.m.) |
Issued | 22 years, 11 months ago (Sept. 18, 2002) |
Published | 22 years, 11 months ago (Sept. 18, 2002) |
Published Online | 22 years, 11 months ago (Sept. 18, 2002) |
Published Print | 22 years, 10 months ago (Oct. 1, 2002) |
@article{David_2002, title={Proteasomal degradation of tau protein}, volume={83}, ISSN={1471-4159}, url={http://dx.doi.org/10.1046/j.1471-4159.2002.01137.x}, DOI={10.1046/j.1471-4159.2002.01137.x}, number={1}, journal={Journal of Neurochemistry}, publisher={Wiley}, author={David, Della C. and Layfield, Robert and Serpell, Louise and Narain, Yolanda and Goedert, Michel and Spillantini, Maria Grazia}, year={2002}, month=sep, pages={176–185} }