Ubiquitination of E3 ubiquitin ligase TRIM5α and its potential role

被引:95
作者
Yamauchi, Keiko [1 ]
Wada, Keiji [1 ]
Tanji, Kunikazu [1 ]
Tanaka, Makoto [1 ]
Kamitani, Tetsu [1 ]
机构
[1] Univ Texas MD Anderson Canc Ctr, Dept Cardiol, Unit 1101, Houston, TX 77030 USA
关键词
ligase; Ro52; TRIM5; ubiquitin; YopJ;
D O I
10.1111/j.1742-4658.2008.06313.x
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
HIV-1 efficiently infects susceptible cells and causes AIDS in humans. Although HIV can also enter the cells of Old World monkeys, it encounters a block before reverse transcription. Data have shown that this species-specific restriction is mediated by tripartite motif (TRIM)5 alpha, whose molecular function is still undefined. Here, we show that TRIM5 alpha functions as a RING-finger-type E3 ubiquitin ligase both in vitro and in vivo and ubiquitinates itself in cooperation with the E2 ubiquitin-conjugating enzyme UbcH5B. In addition to the self-ubiquitination, we show that TRIM5 alpha is ubiquitinated by another E3 ubiquitin ligase, Ro52, and deubiquitinated by YopJ, one of the pathogenic proteins derived from Yersinia species. Thus, the ubiquitination of TRIM5 alpha is catalyzed by itself and Ro52 and downregulated by YopJ. Unexpectedly, although TRIM5 alpha is ubiquitinated, our results have revealed that the proteasome inhibitors MG115 and MG132 do not stabilize it in HeLa cells, suggesting that the ubiquitination of TRIM5 alpha does not lead to proteasomal degradation. Importantly, TRIM5 alpha is clearly conjugated by a single ubiquitin molecule (monoubiquitination). Our monoubiquitin-fusion assay suggests that monoubiquitination is a signal for TRIM5 alpha to translocate from cytoplasmic bodies to the cytoplasm.
引用
收藏
页码:1540 / 1555
页数:16
相关论文
共 41 条
[21]   Differential regulation of Rad18 through Rad6-dependent mono- and polyubiquitination [J].
Miyase, S ;
Tateishi, S ;
Watanabe, K ;
Tomita, K ;
Suzuki, K ;
Inoue, H ;
Yamaizumi, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (01) :515-524
[22]  
POLO S, 2003, SCI STKE, pRE17, DOI DOI 10.1126/STKE.2132003RE17
[23]   The tripartite motif family identifies cell compartments [J].
Reymond, A ;
Meroni, G ;
Fantozzi, A ;
Merla, G ;
Cairo, S ;
Luzi, L ;
Riganelli, D ;
Zanaria, E ;
Messali, S ;
Cainarca, S ;
Guffanti, A ;
Minucci, S ;
Pelicci, PG ;
Ballabio, A .
EMBO JOURNAL, 2001, 20 (09) :2140-2151
[24]   The 52 000 MW Ro/SS-A autoantigen in Sjogren's syndrome/systemic lupus erythematosus (Ro52) is an interferon-γ inducible tripartite motif protein associated with membrane proximal structures [J].
Rhodes, DA ;
Ihrke, G ;
Reinicke, AT ;
Malcherek, G ;
Towey, M ;
Isenberg, DA ;
Trowsdale, J .
IMMUNOLOGY, 2002, 106 (02) :246-256
[25]  
Saurin AJ, 1996, TRENDS BIOCHEM SCI, V21, P208, DOI 10.1016/S0968-0004(96)80017-X
[26]   TRIM5a selectively binds a restriction-sensitive retroviral capsid [J].
Sebastian, S ;
Luban, J .
RETROVIROLOGY, 2005, 2 (1)
[27]   Specific recognition and accelerated uncoating of retroviral capsids by the TRIM5α restriction factor [J].
Stremlau, M ;
Perron, M ;
Lee, M ;
Li, Y ;
Song, B ;
Javanbakht, H ;
Diaz-Griffero, F ;
Anderson, DJ ;
Sundquist, WI ;
Sodroski, J .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (14) :5514-5519
[28]   The cytoplasmic body component TRIM5α restricts HIV-1 infection in Old World monkeys [J].
Stremlau, M ;
Owens, CM ;
Perron, MJ ;
Kiessling, M ;
Autissier, P ;
Sodroski, J .
NATURE, 2004, 427 (6977) :848-853
[29]   Two B or not two B? Overview of the rapidly expanding B-box family of proteins [J].
Torok, M ;
Etkin, LD .
DIFFERENTIATION, 2001, 67 (03) :63-71
[30]   Enhanced Mdm2 activity inhibits pRB function via ubiquitin-dependent degradation [J].
Uchida, CH ;
Miwa, SC ;
Kitagawa, K ;
Hattori, T ;
Isobe, T ;
Otani, S ;
Kamijo, T ;
Ookawa, K ;
Yasuda, H ;
Kitagawa, M ;
Oda, T ;
Sugimura, H .
EMBO JOURNAL, 2005, 24 (01) :160-169