HIV-1 Tat inhibits the 20 S proteasome and its 11 S regulator-mediated activation

被引:95
作者
Seeger, M
Ferrell, K
Frank, R
Dubiel, W
机构
[1] HUMBOLDT UNIV BERLIN,FAC MED,INST BIOCHEM,D-10117 BERLIN,GERMANY
[2] UNIV HEIDELBERG,ZENTRUM MOLEK BIOL HEIDELBERG,D-69120 HEIDELBERG,GERMANY
关键词
D O I
10.1074/jbc.272.13.8145
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
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.
引用
收藏
页码:8145 / 8148
页数:4
相关论文
共 27 条
[1]  
CHU-PING M, 1992, Journal of Biological Chemistry, V267, P10515
[2]   MOLECULAR-CLONING AND EXPRESSION OF SUBUNIT-12 - A NON-MCP AND NON-ATPASE SUBUNIT OF THE 26-S-PROTEASE [J].
DUBIEL, W ;
FERRELL, K ;
DUMDEY, R ;
STANDERA, S ;
PREHN, S ;
RECHSTEINER, M .
FEBS LETTERS, 1995, 363 (1-2) :97-100
[3]   SUBUNITS OF THE REGULATORY COMPLEX OF THE 26S PROTEASE [J].
DUBIEL, W ;
FERRELL, K ;
RECHSTEINER, M .
MOLECULAR BIOLOGY REPORTS, 1995, 21 (01) :27-34
[4]   HBX PROTEIN OF HEPATITIS-B VIRUS INTERACTS WITH THE C-TERMINAL PORTION OF A NOVEL HUMAN PROTEASOME ALPHA-SUBUNIT [J].
FISCHER, M ;
RUNKEL, L ;
SCHALLER, H .
VIRUS GENES, 1995, 10 (01) :99-102
[5]   CELLULAR UPTAKE OF THE TAT PROTEIN FROM HUMAN IMMUNODEFICIENCY VIRUS [J].
FRANKEL, AD ;
PABO, CO .
CELL, 1988, 55 (06) :1189-1193
[6]   Activation of HIV transcription by Tat [J].
Frankel, Alan D. .
CURRENT OPINION IN GENETICS & DEVELOPMENT, 1992, 2 (02) :293-298
[7]   A role for the proteasome regulator PA28 alpha in antigen presentation [J].
Groettrup, M ;
Soza, A ;
Eggers, M ;
Kuehn, L ;
Dick, TP ;
Schild, H ;
Rammensee, HG ;
Koszinowski, UH ;
Kloetzel, PM .
NATURE, 1996, 381 (6578) :166-168
[8]   UBIQUITIN, PROTEASOMES, AND THE REGULATION OF INTRACELLULAR PROTEIN-DEGRADATION [J].
HOCHSTRASSER, M .
CURRENT OPINION IN CELL BIOLOGY, 1995, 7 (02) :215-223
[9]  
HOFFMAN L, 1994, J BIOL CHEM, V269, P16890
[10]  
HOUGH R, 1986, J BIOL CHEM, V261, P2400