Bilateral inhibition of HAUSP deubiquitinase by a viral interferon regulatory factor protein
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Lee, Hye-Ra | - |
dc.contributor.author | Choi, Won-Chan | - |
dc.contributor.author | Lee, Stacy | - |
dc.contributor.author | Hwang, Jungwon | - |
dc.contributor.author | Hwang, Eunha | - |
dc.contributor.author | Guchhait, Koushik | - |
dc.contributor.author | Haas, Juergen | - |
dc.contributor.author | Toth, Zsolt | - |
dc.contributor.author | Jeon, Young Ho | - |
dc.contributor.author | Oh, Tae-Kwang | - |
dc.contributor.author | Kim, Myung Hee | - |
dc.contributor.author | Jung, Jae U. | - |
dc.date.accessioned | 2021-09-07T05:32:45Z | - |
dc.date.available | 2021-09-07T05:32:45Z | - |
dc.date.created | 2021-06-19 | - |
dc.date.issued | 2011-12 | - |
dc.identifier.issn | 1545-9993 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/111003 | - |
dc.description.abstract | Herpesvirus-associated ubiquitin-specific protease (HAUSP) regulates the stability of p53 and the p53-binding protein MDM2, implicating HAUSP as a therapeutic target for tuning p53-mediated antitumor activity. Here we report the structural analysis of HAUSP with Kaposi's sarcoma-associated herpesvirus viral interferon (IFN) regulatory factor 4 (vIRF4) and the discovery of two vIRF4-derived peptides, vif1 and vif2, as potent and selective HAUSP antagonists. This analysis reveals a bilateral belt-type interaction that results in inhibition of HAUSP. The vif1 peptide binds the HAUSP TRAF domain, competitively blocking substrate binding, whereas the vif2 peptide binds both the HAUSP TRAF and catalytic domains, robustly suppressing its deubiquitination activity. Peptide treatments comprehensively blocked HAUSP, leading to p53-dependent cell-cycle arrest and apoptosis in culture and to tumor regression in xenograft mouse model. Thus, the virus has developed a unique strategy to target the HAUSP-MDM2-p53 pathway, and these virus-derived short peptides represent biologically active HAUSP antagonists. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | NATURE PUBLISHING GROUP | - |
dc.subject | UBIQUITIN-SPECIFIC PROTEASE | - |
dc.subject | NUCLEAR ANTIGEN | - |
dc.subject | P53 | - |
dc.subject | LYMPHOMAS | - |
dc.subject | MDM2 | - |
dc.subject | RESTORATION | - |
dc.subject | ACETYLATION | - |
dc.subject | RECOGNITION | - |
dc.subject | REQUIREMENT | - |
dc.subject | EXPRESSION | - |
dc.title | Bilateral inhibition of HAUSP deubiquitinase by a viral interferon regulatory factor protein | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Lee, Hye-Ra | - |
dc.contributor.affiliatedAuthor | Jeon, Young Ho | - |
dc.identifier.doi | 10.1038/nsmb.2142 | - |
dc.identifier.scopusid | 2-s2.0-82955187316 | - |
dc.identifier.wosid | 000298011600019 | - |
dc.identifier.bibliographicCitation | NATURE STRUCTURAL & MOLECULAR BIOLOGY, v.18, no.12, pp.1336 - U48 | - |
dc.relation.isPartOf | NATURE STRUCTURAL & MOLECULAR BIOLOGY | - |
dc.citation.title | NATURE STRUCTURAL & MOLECULAR BIOLOGY | - |
dc.citation.volume | 18 | - |
dc.citation.number | 12 | - |
dc.citation.startPage | 1336 | - |
dc.citation.endPage | U48 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Biophysics | - |
dc.relation.journalResearchArea | Cell Biology | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Biophysics | - |
dc.relation.journalWebOfScienceCategory | Cell Biology | - |
dc.subject.keywordPlus | UBIQUITIN-SPECIFIC PROTEASE | - |
dc.subject.keywordPlus | NUCLEAR ANTIGEN | - |
dc.subject.keywordPlus | P53 | - |
dc.subject.keywordPlus | LYMPHOMAS | - |
dc.subject.keywordPlus | MDM2 | - |
dc.subject.keywordPlus | RESTORATION | - |
dc.subject.keywordPlus | ACETYLATION | - |
dc.subject.keywordPlus | RECOGNITION | - |
dc.subject.keywordPlus | REQUIREMENT | - |
dc.subject.keywordPlus | EXPRESSION | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
145 Anam-ro, Seongbuk-gu, Seoul, 02841, Korea+82-2-3290-2963
COPYRIGHT © 2021 Korea University. All Rights Reserved.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.