Furin cleavage of the HIV-1 tat protein

被引：23

作者：

Tikhonov, I ^{[1
]}

Ruckwardt, TJ ^{[1
]}

Berg, S ^{[1
]}

Hatfield, GS ^{[1
]}

Pauza, CD ^{[1
]}

机构：

[1] Univ Maryland, Inst Biotechnol, Inst Human Virol, Baltimore, MD 21201 USA

来源：

FEBS LETTERS | 2004年 / 565卷 / 1-3期

关键词：

Tat; HIV; furin; protease; processing;

D O I：

10.1016/j.febslet.2004.03.079

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Extracellular human immunodeficiency virus-1 (HIV-1) Tat protein and Tat-derived peptides are biologically active but mechanisms of Tat processing are not known. Within the highly conserved basic region of HIV-1 Tat protein (amino acids, a.a. 48-56), we identified two putative furin cleavage sites and showed that Tat protein was cleaved in vitro at the second site, RQRRdown arrow (a.a. 53-56down arrow). This in vitro cleavage was blocked by a monoclonal antibody that binds near the cleavage site or by the furin inhibitor alpha-1 PDX. Monocytoid cells rich in furin also degraded Tat and this process was slowed by the furin inhibitor or the specific monoclonal antibody. Furin processing did not affect the rates for Tat uptake ad nuclear accumulation in HeLa or Jurkat cells, but the transactivation activity was greatly reduced. Furin processing is a likely mechanism for inactivating extracellular HIV-1 Tat protein. (C) 2004 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.

引用

页码：89 / 92

页数：4

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