title: Ubiquitination of E3 ubiquitin ligase TRIM5 alpha and its potential role.
abstract: 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)5alpha, whose molecular function is still undefined. Here, we show that TRIM5alpha 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 TRIM5alpha 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 TRIM5alpha is catalyzed by itself and Ro52 and downregulated by YopJ. Unexpectedly, although TRIM5alpha 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 TRIM5alpha does not lead to proteasomal degradation. Importantly, TRIM5alpha is clearly conjugated by a single ubiquitin molecule (monoubiquitination). Our monoubiquitin-fusion assay suggests that monoubiquitination is a signal for TRIM5alpha to translocate from cytoplasmic bodies to the cytoplasm.
authors.affiliation: Department of Cardiology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Keiko
authors.initials: K
authors.lastname: Yamauchi
authors.affiliation: Department of Cardiology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Keiji
authors.initials: K
authors.lastname: Wada
authors.affiliation: Department of Cardiology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Kunikazu
authors.initials: K
authors.lastname: Tanji
authors.affiliation: Department of Cardiology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Makoto
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Department of Cardiology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Tetsu
authors.initials: T
authors.lastname: Kamitani
mesh_terms: D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism* / Q000502:physiology; D002460:Cell Line; D003593:Cytoplasm / Q000201:enzymology; D019143:Evolution, Molecular; D006367:HeLa Cells; D006801:Humans; D010802:Phylogeny; D012261:Ribonucleoproteins / Q000737:chemistry; D000070584:Tripartite Motif Proteins; D025801:Ubiquitin / Q000378:metabolism*; D044763:Ubiquitin-Conjugating Enzymes / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000378:metabolism*; D000099207:SS-A Antigen
chemical_list: D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; D012261:Ribonucleoproteins; D000070584:Tripartite Motif Proteins; D025801:Ubiquitin; D044763:Ubiquitin-Conjugating Enzymes; D044767:Ubiquitin-Protein Ligases; D000099207:SS-A Antigen; C097309:UBE2D2 protein, human; C477346:TRIM5 protein, human