HIV-1 tat inhibits the 20 S proteasome and its 11 S regulator-mediated activation.
The proteasomal system consists of a proteolytic core, the 20 S proteasome, which associates in an ATP-dependent reaction with the 19 S regulatory complex to form the functional 26 S proteasome. In the absence of ATP, the 20 S proteasome forms a complex with the gamma-interferon-inducible 11 S regulator. Both the 20 S proteasome and the 11 S regulator have been implied in the generation of antigenic peptides. The human immunodeficiency virus (HIV)-1 Tat protein causes a number of different effects during acquired immunodeficiency syndrome (AIDS). Here we show that HIV-1 Tat protein strongly inhibits the peptidase activity of the 20 S proteasome and that it interferes with formation of the 20 S proteasome-11 S regulator complex. In addition, it slightly increases the activity of purified 26 S proteasome. These results may explain the mechanism by which HIV-1-infected cells escape cytotoxic T lymphocyte response and at least in part immunodeficiency in AIDS patients.
Seeger
M
M
Institute of Biochemistry, Humboldt-University, Medical Faculty (Charité), Monbijoustrasse 2A, 10117 Berlin, Germany.
Ferrell
K
K
Frank
R
R
Dubiel
W
W
D000074183:ATPases Associated with Diverse Cellular Activities; D015153:Blotting, Western; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000494:pharmacology*; D004789:Enzyme Activation; D005456:Fluorescent Dyes / Q000378:metabolism; D015497:HIV-1; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D009097:Multienzyme Complexes / Q000378:metabolism*; D009124:Muscle Proteins; D010455:Peptides / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D011487:Protein Conformation; D011506:Proteins / Q000378:metabolism*
D004268:DNA-Binding Proteins; D005456:Fluorescent Dyes; D009097:Multienzyme Complexes; D009124:Muscle Proteins; C085047:PSME1 protein, human; D010455:Peptides; D011506:Proteins; C075363:PSMC2 protein, human; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D000074183:ATPases Associated with Diverse Cellular Activities; C064757:PSMC3 protein, human