Screen for ISG15-crossreactive Deubiquitinases

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Screen for ISG15-crossreactive Deubiquitinases

Show simple item record Catic, Andre Fiebiger, Edda Korbel, Gregory Blom, Daniël Galardy, Paul J. Ploegh, Hidde L. 2011-03-01T04:52:39Z 2007
dc.identifier.citation Catic, André, Edda Fiebiger, Gregory A. Korbel, Daniël Blom, Paul J. Galardy, and Hidde L. Ploegh. 2007. Screen for ISG15-crossreactive Deubiquitinases. PLoS ONE 2(7): e679. en_US
dc.identifier.issn 1932-6203 en_US
dc.description.abstract Background: The family of ubiquitin-like molecules (UbLs) comprises several members, each of which has sequence, structural, or functional similarity to ubiquitin. ISG15 is a homolog of ubiquitin in vertebrates and is strongly upregulated following induction by type I interferon. ISG15 can be covalently attached to proteins, analogous to ubiquitination and with actual support of ubiquitin conjugating factors. Specific proteases are able to reverse modification with ubiquitin or UbLs by hydrolyzing the covalent bond between their C-termini and substrate proteins. The tail regions of ubiquitin and ISG15 are identical and we therefore hypothesized that promiscuous deubiquitinating proteases (DUBs) might exist, capable of recognizing both ubiquitin and ISG15. Results: We have cloned and expressed 22 human DUBs, representing the major clades of the USP protease family. Utilizing suicide inhibitors based on ubiquitin and ISG15, we have identified USP2, USP5 (IsoT1), USP13 (IsoT3), and USP14 as ISG15-reactive proteases, in addition to the bona fide ISG15-specific protease USP18 (UBP43). USP14 is a proteasome-associated DUB, and its ISG15 isopeptidase activity increases when complexed with the proteasome. Conclusions: By evolutionary standards, ISG15 is a newcomer among the UbLs and it apparently not only utilizes the conjugating but also the deconjugating machinery of its more established relative ubiquitin. Functional overlap between these two posttranslational modifiers might therefore be more extensive than previously appreciated and explain the rather innocuous phenotype of ISG15 null mice. en_US
dc.language.iso en_US en_US
dc.publisher Public Library of Science en_US
dc.relation.isversionof doi:10.1371/journal.pone.0000679 en_US
dc.relation.hasversion en_US
dash.license LAA
dc.subject biochemistry en_US
dc.subject oncology en_US
dc.subject biotechnology en_US
dc.subject protein chemistry and proteomics en_US
dc.title Screen for ISG15-crossreactive Deubiquitinases en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal PLoS ONE en_US Fiebiger, Edda 2011-03-01T04:52:39Z
dash.affiliation.other HMS^Medicine-Massachusetts General Hospital en_US

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