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Article: Id-1 Induces Proteasome-dependent Degradation of the HBX Protein

TitleId-1 Induces Proteasome-dependent Degradation of the HBX Protein
Authors
KeywordsC8
degradation
HBX
Id-1
proteasome
Issue Date2008
PublisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/jmb
Citation
Journal Of Molecular Biology, 2008, v. 382 n. 1, p. 34-43 How to Cite?
AbstractId-1 is a member of the HLH protein family that regulates a wide range of cellular processes such as cell proliferation, apoptosis, senescence and overexpression of Id-1 was recently suggested to play roles in the development and progression of different cancers. Previously, Id-1 was shown to physically interact with the viral protein E1A. Meanwhile, Id-1 expression was found to be regulated by several of the virus-encoded proteins, suggesting that Id-1 may be a common cellular target of the viral proteins. Here, we report that Id-1 interacts with the Hepatitis-B virus (HBV)-encoded protein HBX and regulates its stability in hepatocellular carcinoma (HCC) cells. We found that in HCC cells, ectopic Id-1 expression significantly decreased the half-life of the HBX protein, indicating that HBX is destabilized by Id-1. Meanwhile, the Id-1-induced HBX degradation was found to be inhibited by treatment with proteasome inhibitor, suggesting that this process is mediated through the proteasome pathway. Interestingly, while Id-1 did not induce HBX-ubiquitination, we found that removal of all the lysine residues of the HBX protein protects it from the effect of Id-1, indicating that ubiquitination is still required for the Id-1-mediated HBX degradation. Meanwhile, we found that Id-1 binds to the proteasome subunit C8 and facilitates its interaction with the HBX protein and disruption of this interaction completely abolishes the negative effect of Id-1 on HBX protein stability. Taken together, our results demonstrated a novel function of Id-1 in regulating HBX protein stability through interaction with the proteasome. © 2007 Elsevier Ltd. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/58232
ISSN
2015 Impact Factor: 4.517
2015 SCImago Journal Rankings: 3.002
ISI Accession Number ID
Funding AgencyGrant Number
RGCHKU7490/03M
HKU7470/04M
HKU7478/03M
Funding Information:

This work was supported by RGC grants to Y. C. W. (HKU7490/03M, HKU7470/04M) and to X. W. (HKU7478/03M).

References

 

DC FieldValueLanguage
dc.contributor.authorLing, MTen_HK
dc.contributor.authorChiu, YTen_HK
dc.contributor.authorLee, TKWen_HK
dc.contributor.authorLeung, SCLen_HK
dc.contributor.authorFung, MKLen_HK
dc.contributor.authorWang, Xen_HK
dc.contributor.authorWong, KFen_HK
dc.contributor.authorWong, YCen_HK
dc.date.accessioned2010-05-31T03:26:17Z-
dc.date.available2010-05-31T03:26:17Z-
dc.date.issued2008en_HK
dc.identifier.citationJournal Of Molecular Biology, 2008, v. 382 n. 1, p. 34-43en_HK
dc.identifier.issn0022-2836en_HK
dc.identifier.urihttp://hdl.handle.net/10722/58232-
dc.description.abstractId-1 is a member of the HLH protein family that regulates a wide range of cellular processes such as cell proliferation, apoptosis, senescence and overexpression of Id-1 was recently suggested to play roles in the development and progression of different cancers. Previously, Id-1 was shown to physically interact with the viral protein E1A. Meanwhile, Id-1 expression was found to be regulated by several of the virus-encoded proteins, suggesting that Id-1 may be a common cellular target of the viral proteins. Here, we report that Id-1 interacts with the Hepatitis-B virus (HBV)-encoded protein HBX and regulates its stability in hepatocellular carcinoma (HCC) cells. We found that in HCC cells, ectopic Id-1 expression significantly decreased the half-life of the HBX protein, indicating that HBX is destabilized by Id-1. Meanwhile, the Id-1-induced HBX degradation was found to be inhibited by treatment with proteasome inhibitor, suggesting that this process is mediated through the proteasome pathway. Interestingly, while Id-1 did not induce HBX-ubiquitination, we found that removal of all the lysine residues of the HBX protein protects it from the effect of Id-1, indicating that ubiquitination is still required for the Id-1-mediated HBX degradation. Meanwhile, we found that Id-1 binds to the proteasome subunit C8 and facilitates its interaction with the HBX protein and disruption of this interaction completely abolishes the negative effect of Id-1 on HBX protein stability. Taken together, our results demonstrated a novel function of Id-1 in regulating HBX protein stability through interaction with the proteasome. © 2007 Elsevier Ltd. All rights reserved.en_HK
dc.languageengen_HK
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/jmben_HK
dc.relation.ispartofJournal of Molecular Biologyen_HK
dc.subjectC8en_HK
dc.subjectdegradationen_HK
dc.subjectHBXen_HK
dc.subjectId-1en_HK
dc.subjectproteasomeen_HK
dc.subject.meshCell Line, Tumoren_HK
dc.subject.meshHumansen_HK
dc.subject.meshInhibitor of Differentiation Protein 1 - chemistry - metabolismen_HK
dc.subject.meshProteasome Endopeptidase Complex - metabolismen_HK
dc.subject.meshProtein Bindingen_HK
dc.subject.meshProtein Processing, Post-Translationalen_HK
dc.subject.meshProtein Structure, Tertiaryen_HK
dc.subject.meshProtein Subunits - metabolismen_HK
dc.subject.meshThermodynamicsen_HK
dc.subject.meshTrans-Activatorsen_HK
dc.subject.meshUbiquitinationen_HK
dc.subject.meshViral Regulatory and Accessory Proteins - chemistry - metabolismen_HK
dc.titleId-1 Induces Proteasome-dependent Degradation of the HBX Proteinen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0022-2836&volume=382&spage=34&epage=43&date=2008&atitle=Id-1+induces+proteasome-dependent+degradation+of+the+HBX+proteinen_HK
dc.identifier.emailLing, MT:patling@hkucc.hku.hken_HK
dc.identifier.emailLee, TKW:tkwlee@hkucc.hku.hken_HK
dc.identifier.emailWong, YC:ycwong@hkucc.hku.hken_HK
dc.identifier.authorityLing, MT=rp00449en_HK
dc.identifier.authorityLee, TKW=rp00447en_HK
dc.identifier.authorityWong, YC=rp00316en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.jmb.2007.06.020en_HK
dc.identifier.pmid18674781-
dc.identifier.scopuseid_2-s2.0-49349107931en_HK
dc.identifier.hkuros150520en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-49349107931&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume382en_HK
dc.identifier.issue1en_HK
dc.identifier.spage34en_HK
dc.identifier.epage43en_HK
dc.identifier.isiWOS:000259588500004-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridLing, MT=7102229780en_HK
dc.identifier.scopusauthoridChiu, YT=23975797700en_HK
dc.identifier.scopusauthoridLee, TKW=7501439435en_HK
dc.identifier.scopusauthoridLeung, SCL=36894169100en_HK
dc.identifier.scopusauthoridFung, MKL=8718040400en_HK
dc.identifier.scopusauthoridWang, X=7501854829en_HK
dc.identifier.scopusauthoridWong, KF=35081410800en_HK
dc.identifier.scopusauthoridWong, YC=7403041798en_HK

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