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dc.contributor.authorSivakumaran, Haran
dc.contributor.authorvan der Horst, Armando
dc.contributor.authorJ. Fulcher, Alex
dc.contributor.authorApolloni, Ann
dc.contributor.authorLin, Min-Hsuan
dc.contributor.authorA. Jans, David
dc.contributor.authorHarrich, David
dc.date.accessioned2017-09-04T03:30:29Z
dc.date.available2017-09-04T03:30:29Z
dc.date.issued2009
dc.date.modified2010-06-23T05:23:00Z
dc.identifier.issn0022538X
dc.identifier.doi10.1128/JVI.00499-09
dc.identifier.urihttp://hdl.handle.net/10072/30220
dc.description.abstractArginine methylation of human immunodeficiency virus type 1 (HIV-1) Tat protein downregulates its key function in viral-gene transactivation. The fate of methylated Tat is unknown, so it is unclear whether methylated Tat is degraded or persists in the cell for additional functions. Here we show that the arginine methyltransferase PRMT6 increases Tat protein half-life by 4.7-fold. Tat stabilization depends on the catalytic activity of PRMT6 and requires arginine methylation within the Tat basic domain. In contrast, HIV-1 Rev, which is also methylated by PRMT6, is completely refractory to the stabilizing effect. Proteasome inhibition and silencing experiments demonstrated that Tat can be degraded by a REG -independent proteasome, against which PRMT6 appears to act to increase Tat half-life. Our data reveal a proteasome-dependent Tat degradation pathway that is inhibited by arginine methylation. The stabilizing action of PRMT6 could allow Tat to persist within the cell and the extracellular environment and thereby enable functions implicated in AIDS-related cancer, neurodegeneration, and T-cell death.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherAmerican Society for Microbiology.
dc.publisher.placeUnited States
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom11694
dc.relation.ispartofpageto11703
dc.relation.ispartofissue22
dc.relation.ispartofjournalJournal of Virology
dc.relation.ispartofvolume83
dc.rights.retentionY
dc.subject.fieldofresearchMedical Microbiology not elsewhere classified
dc.subject.fieldofresearchMicrobiology not elsewhere classified
dc.subject.fieldofresearchBiological Sciences
dc.subject.fieldofresearchAgricultural and Veterinary Sciences
dc.subject.fieldofresearchMedical and Health Sciences
dc.subject.fieldofresearchcode110899
dc.subject.fieldofresearchcode060599
dc.subject.fieldofresearchcode06
dc.subject.fieldofresearchcode07
dc.subject.fieldofresearchcode11
dc.titleArginine Methylation Increases the Stability of Human Immunodeficiency Virus Type 1 Tat
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© 2009 American Society for Microbiology. The attached file is reproduced here in accordance with the copyright policy of the publisher. Please refer to the journal's website for access to the definitive, published version.
gro.date.issued2009
gro.hasfulltextFull Text
gro.griffith.authorHarrich, David


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