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

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.

journal_name

J Virol

journal_title

Journal of virology

authors

Sivakumaran H,van der Horst A,Fulcher AJ,Apolloni A,Lin MH,Jans DA,Harrich D

doi

10.1128/JVI.00499-09

subject

Has Abstract

pub_date

2009-11-01 00:00:00

pages

11694-703

issue

22

eissn

0022-538X

issn

1098-5514

pii

JVI.00499-09

journal_volume

83

pub_type

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