Regulation of Proteasome Activity by Ubiquitin Chain Editing
Event Details
- Type
- Friday Lecture Series
- Speaker(s)
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Daniel Finley, Ph.D., professor, department of cell biology, Harvard Medical School
- Speaker bio(s)
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Proteasomes contain conserved activities that can edit multiubiquitin chains on substrates: the deubiquitinating enzyme Ubp6/Usp14 and the ubiquitin ligase Hul5/Ube3C. Ubp6/Usp14, by attacking ubiquitin chains, suppresses degradation, while Hul5/Ube3c, an autism factor, promotes it by adding ubiquitin groups. The deubiquitinating activity of Usp14 can be suppressed by highly specific small-molecule inhibitors identified by high-throughput screening. These compounds, administered at levels that do not impair cell viability, allow one to selectively enhance the degradation rates of various proteins, including some that have been implicated in neurodegeneration. Substrates vary dramatically in their susceptibility to Usp14 inhibition. Surprisingly, a key determinant of Usp14’s substrate specificity is the number of ubiquitin chains on the substrate, rather than the number of ubiquitins. For substrates tested, Usp14 will not act when only a single ubiquitin chain is present on the substrate, a principle of selectivity that is believed to be completely novel. The attack on supernumerary chains may have a substantial impact on the overall selectivity of protein degradation by the proteasome, biasing degradation towards single-chain substrates produced by highly processive ubiquitin ligases.
Dr. Finley received his Ph.D. from the Massachusetts Institute of Technology in 1984, where he did his thesis work with Alex Varshavksy. He completed postdoctoral training from 1984 to 1988 at MIT. Dr. Finley was appointed to the faculty of Harvard Medical School in 1988 and since 2000 has been a professor in the department of cell biology. - Open to
- Public
- Reception
- Refreshments, 3:15 p.m. - 3:45 p.m., Abby Lounge
- Contact
- Alena Powell
- Phone
- (212) 327-7745
- Sponsor
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Alena Powell
(212) 327-7745
apowell@rockefeller.edu - Readings
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http://librarynews.rockefeller.edu/?p=3502