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Furin cleavage of the HIV‐1 Tat protein
Author(s) -
Tikhonov Ilia,
Ruckwardt Tracy J.,
Berg Shan,
Hatfield Glen S.,
David Pauza C.
Publication year - 2004
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2004.03.079
Subject(s) - furin , cleavage (geology) , monoclonal antibody , extracellular , jurkat cells , in vitro , microbiology and biotechnology , hela , chemistry , biochemistry , transactivation , biology , antibody , enzyme , t cell , gene expression , immunology , gene , paleontology , immune system , fracture (geology)
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, RQRR↓ (a.a. 53–56↓). This in vitro cleavage was blocked by a monoclonal antibody that binds near the cleavage site or by the furin inhibitor α‐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 and 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.