Arginine methylation increases the stability of HIV-1 Tat

Sivakumaran, Haran, van der Horst, Armando, Fulcher, Alex J., Apolloni, Ann, Lin, Min-Hsuan, Jans, David A. and Harrich, David (2009) Arginine methylation increases the stability of HIV-1 Tat. Journal of Virology, 83 22: 11694-11703. doi:10.1128/JVI.00499-09

Author Sivakumaran, Haran
van der Horst, Armando
Fulcher, Alex J.
Apolloni, Ann
Lin, Min-Hsuan
Jans, David A.
Harrich, David
Title Arginine methylation increases the stability of HIV-1 Tat
Journal name Journal of Virology   Check publisher's open access policy
ISSN 0022-538X
Publication date 2009-11
Sub-type Article (original research)
DOI 10.1128/JVI.00499-09
Open Access Status DOI
Volume 83
Issue 22
Start page 11694
End page 11703
Total pages 10
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Language eng
Subject 060506 Virology
060107 Enzymes
060109 Proteomics and Intermolecular Interactions (excl. Medical Proteomics)
Formatted abstract
Arginine 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. HIV-1 Rev, in contrast, 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 REGγ-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 extracellular environment and thereby enable functions implicated in AIDS-related cancer, neurodegeneration and T cell death.
Keyword HIV
Protein Stability
Arginine Methylation
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Faculty of Health and Behavioural Sciences -- Student Publications
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School of Public Health Publications
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Created: Mon, 07 Sep 2009, 18:03:30 EST by Dhivakaren (Haran) Sivakumaran on behalf of School of Public Health