Open-gate mutants of the mammalian proteasome show enhanced ubiquitin-conjugate degradation

Title
Open-gate mutants of the mammalian proteasome show enhanced ubiquitin-conjugate degradation
Authors
최원훈Stefanie A.H. de Poot이정훈김지현한동훈김윤경Dniel Finley이민재
Keywords
타우; 프로테오좀
Issue Date
2016-03
Publisher
Nature Communications
Abstract
When in the closed form, the substrate translocation channel of the proteasome core particle CP) is blocked by the convergent N termini of a-subunits. To probe the role of channel gating in mammalian proteasomes, we deleted the N-terminal tail of a3; the resulting a3DN proteasomes are intact but hyperactive in the hydrolysis of fluorogenic peptide substrates and the degradation of polyubiquitinated proteins. Cells expressing the hyperactive proteasomes show markedly elevated degradation of many established proteasome substrates and resistance to oxidative stress. Multiplexed quantitative proteomics revealed B200 proteins with reduced levels in the mutant cells. Potentially toxic proteins such as tau exhibit reduced accumulation and aggregate formation. These data demonstrate that the CP gate is a key negative regulator of proteasome function in mammals, and that opening the CP gate may be an effective strategy to increase proteasome activity and reduce levels of toxic proteins in cells.
URI
http://pubs.kist.re.kr/handle/201004/58790
ISSN
20411723
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KIST Publication > Article
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