You are not currently logged in.
Access JSTOR through your library or other institution:
If You Use a Screen ReaderThis content is available through Read Online (Free) program, which relies on page scans. Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
CHIP Regulates Leucine-Rich Repeat Kinase-2 Ubiquitination, Degradation, and Toxicity
Han Seok Ko, Rachel Bailey, Wanli W. Smith, Zhaohui Liu, Joo-Ho Shin, Yun-Il Lee, Yong-Jie Zhang, Haibing Jiang, Christopher A. Ross, Darren J. Moore, Cam Patterson, Leonard Petrucelli, Ted M. Dawson, Valina L. Dawson and Solomon H. Snyder
Proceedings of the National Academy of Sciences of the United States of America
Vol. 106, No. 8 (Feb. 24, 2009), pp. 2897-2902
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/40421806
Page Count: 6
You can always find the topics here!Topics: Toxicity, Parkinson disease, Neurons, Genetic mutation, HeLa cells, Ubiquitins, Small interfering RNA, Antibodies, Physiological regulation, Viability
Were these topics helpful?See somethings inaccurate? Let us know!
Select the topics that are inaccurate.
Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Preview not available
Mutation in leucine-rich repeat kinase-2 (LRRK2) is the most common cause of late-onset Parkinson's disease (PD). Although most cases of PD are sporadic, some are inherited, including those caused by LRRK2 mutations. Because these mutations may be associated with a toxic gain of function, controlling the expression of LRRK2 may decrease its cytotoxicity. Here we show that the carboxyl terminus of HSP70-interacting protein (CHIP) binds, ubiquitinates, and promotes the ubiquitin proteasomal degradation of LRRK2. Overexpression of CHIP protects against and knockdown of CHIP exacerbates toxicity mediated by mutant LRRK2. Moreover, HSP90 forms a complex with LRRK2, and inhibition of HSP90 chaperone activity by 17AAG leads to proteasomal degradation of LRRK2, resulting in increased cell viability. Thus, increasing CHIP E3 ligase activity and blocking HSP90 chaperone activity can prevent the deleterious effects of LRRK2. These findings point to potential treatment options for LRRK2-associated PD.
Proceedings of the National Academy of Sciences of the United States of America © 2009 National Academy of Sciences