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Arginine methylation increases the stability of human immunodeficiency virus type 1 Tat.

Authors
  • Sivakumaran, Haran
  • van der Horst, Armando
  • Fulcher, Alex J
  • Apolloni, Ann
  • Lin, Min-Hsuan
  • Jans, David A
  • Harrich, David
Type
Published Article
Journal
Journal of Virology
Publisher
American Society for Microbiology
Publication Date
Nov 01, 2009
Volume
83
Issue
22
Pages
11694–11703
Identifiers
DOI: 10.1128/JVI.00499-09
PMID: 19726520
Source
Medline
License
Unknown

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. 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 REGgamma-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.

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