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Enzymatic blockade of the ubiquitin-proteasome pathway
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نویسنده
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ernst r. ,claessen j.h.l. ,mueller b. ,sanyal s. ,spooner e. ,van der veen a.g. ,kirak o. ,schlieker c.d. ,weihofen w.a. ,ploegh h.l.
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منبع
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plos biology - 2011 - دوره : 9 - شماره : 3
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چکیده
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Ubiquitin-dependent processes control much of cellular physiology. we show that expression of a highly active,epstein-barr virus-derived deubiquitylating enzyme (ebv-dub) blocks proteasomal degradation of cytosolic and er-derived proteins by preemptive removal of ubiquitin from proteasome substrates,a treatment less toxic than the use of proteasome inhibitors. recognition of misfolded proteins in the er lumen,their dislocation to the cytosol,and degradation are usually tightly coupled but can be uncoupled by the ebv-dub: a misfolded glycoprotein that originates in the er accumulates in association with cytosolic chaperones as a deglycosylated intermediate. our data underscore the necessity of a dub activity for completion of the dislocation reaction and provide a new means of inhibition of proteasomal proteolysis with reduced cytotoxicity. © 2011 ernst et al.
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آدرس
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whitehead institute for biomedical research,cambridge,ma,united states,max-planck institute for molecular cell biology and genetics,dresden, Germany, whitehead institute for biomedical research,cambridge,ma, United States, whitehead institute for biomedical research,cambridge,ma,united states,massachusetts general hospital,richard b. simches research center-7,boston,ma, United States, whitehead institute for biomedical research,cambridge,ma, United States, whitehead institute for biomedical research,cambridge,ma, United States, whitehead institute for biomedical research,cambridge,ma, United States, whitehead institute for biomedical research,cambridge,ma, United States, whitehead institute for biomedical research,cambridge,ma,united states,department of molecular biophysics and biochemistry,yale university,new haven,ct, United States, department of molecular and cellular biology,harvard university,cambridge,ma, United States, whitehead institute for biomedical research,cambridge,ma,united states,department of biology,massachusetts institute of technology,cambridge,ma, United States
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Authors
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