TAILIEUCHUNG - Báo cáo khoa học: Ubiquitination of E3 ubiquitin ligase TRIM5a and its potential role

HIV-1 efficiently infects susceptible cells and causes AIDS in humans. Although HIV can also enter the cells of Old World monkeys, it encoun-ters a block before reverse transcription. Data have shown that this species-specific restriction is mediated by tripartite motif (TRIM)5a, whose molecular function is still undefined. | ễFEBS Journal Ubiquitination of E3 ubiquitin ligase TRIM5a and its potential role Keiko Yamauchi Keiji Wada Kunikazu Tanji Makoto Tanaka and Tetsu Kamitani Department of Cardiology The University of Texas M. D. Anderson Cancer Center Houston TX USA Keywords ligase Ro52 TRIM5 ubiquitin YopJ Correspondence T. Kamitani Department of Cardiology The University of Texas . Anderson Cancer Center 1515 Holcombe Blvd. Unit 1101 Houston TX 77030 USA Fax 1 713 563 0424 Tel 1 713 563 0413 E-mail tkamitani@ Received 7 December 2007 revised 24 January 2008 accepted 30 January 2008 doi 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 5a whose molecular function is still undefined. Here we show that TRIM5a 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 TRIM5a 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 TRIM5a is catalyzed by itself and Ro52 and downregulated by YopJ. Unexpectedly although TRIM5a 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 TRIM5a does not lead to proteasomal degradation. Importantly TRIM5a is clearly conjugated by a single ubiquitin molecule monoubiquitination . Our monoubiquitin-fusion assay suggests that mono-ubiquitination is a signal for TRIM5a to translocate from cytoplasmic bodies to the cytoplasm. Host cell barriers to the early phase of immunodeficiency virus replication explain .

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• HIV 1 efficiently infects susceptible cells and causes AIDS in humans
• Although HIV can also enter the cells of Old World monkeys
• it encoun ters a block before reverse transcription
• Data have shown that this species specific restriction is mediated by tripartite motif (TRIM)5a
• whose molecular function is still undefined
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