Extended ubiquitin species are protein-based DUB inhibitors.
Extended ubiquitin species are protein-based DUB inhibitors.
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DOI：
10.1038/nchembio.1574
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发表时间：
2014-08
影响因子：
14.8
通讯作者：
Glickman, Michael H.
中科院分区：
文献类型：
--
作者：
Krutauz, Daria;Reis, Noa;Nakasone, Mark A.;Siman, Peter;Zhang, Daoning;Kirkpatrick, Donald S.;Gygi, Steven P.;Brik, Ashraf;Fushman, David;Glickman, Michael H.
A frame-shift mutation in the transcript of the ubiquitin-B gene leads to a C-terminally extended ubiquitin, UBB+1. UBB+1 has been considered to inhibit proteasomes, and as such to be the underlying cause for toxic protein buildup correlated with certain neuropathological conditions. We demonstrated that expression of extended ubiquitin variants led to accumulation of heterogeneously-linked polyubiquitin conjugates indicating a pervasive effect on ubiquitin-dependent turnover. 20S proteasomes selectively proteolysed ubiquitin extensions, yet no evidence for inhibition of 26S holoenzymes was found. However, among susceptible targets for inhibition was Ubp6, the primary enzyme responsible for disassembly of lysine-48 linkages at 26S proteasomes. Processing of lysine-48 and lysine-63 linkages by other deubiquitinating enzymes (DUBs) was also inhibited. Disruption of ubiquitin-dependent degradation by extended ubiquitin variants may therefore be attributed to their inhibitory effect on select DUBs, thus shifting research efforts related to protein accumulation in neurodegenerative processes from proteasomes to DUBs.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
4.8
作者：
Kirkpatrick, DS;Gerber, SA;Gygi, SP
通讯作者：
Gygi, SP
DOI：
10.1074/mcp.r110.003871
发表时间：
2011-05-01
期刊：
Molecular & cellular proteomics : MCP
影响因子：
--
作者：
Lee, Min Jae;Lee, Byung-Hoon;Finley, Daniel
通讯作者：
Finley, Daniel
影响因子：
5.6
作者：
Datta, Ajit B.;Hura, Greg L.;Wolberger, Cynthia
通讯作者：
Wolberger, Cynthia
影响因子：
11.4
作者：
Fu, HY;Reis, N;Vierstra, RD
通讯作者：
Vierstra, RD