The degradation of promyelocytic leukemia and Sp100 proteins by herpes simplex virus 1 is mediated by the ubiquitin-conjugating enzyme UbcH5a.
Infected cell protein 0 (ICP0) of herpes simplex virus 1 expresses two E3 ubiquitin (Ub) ligase activities mapping in the domains encoded by exons 2 and 3, respectively. Site 1 (exon 3) is responsible for the degradation of the E2 Ub-conjugating enzyme cdc34 whereas site 2 (exon 2) is associated with a ring finger and has been shown to mediate the degradation of promyelocytic leukemia (PML) and Sp100 proteins and the dispersal of nuclear domain 10 (ND10). In in vitro assays site 2 polyubiquitylates the E2 enzymes UbcH5a and UbcH6 but not other (e.g., UbcH7) enzymes. In this article, we show that ectopic expression of dominant negative UbcH5a carrying the substitution C85A delayed or blocked the degradation of PML and Sp100 and dispersal of ND10 whereas ectopic expression of wild-type UbcH5a or dominant negative UbcH6 and UbcH7 carrying the substitutions C131A and C86A, respectively, had no effect. These results link the degradation of PML and Sp100 and the dispersal of ND10 to the E3 activities of ICP0 associated with the UbcH5a E2 enzyme.
Gu
Haidong
H
The Marjorie B. Kovler Viral Oncology Laboratories, University of Chicago, 910 East 58th Street, Chicago, IL 60637, USA.
Roizman
Bernard
B
D019943:Amino Acid Substitution; D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism*; D001324:Autoantigens / Q000378:metabolism*; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D002522:Chlorocebus aethiops; D005091:Exons; D006367:HeLa Cells; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D033862:Iron-Binding Proteins; D008025:Ligases / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors / Q000378:metabolism*; D014161:Transduction, Genetic; D025521:Tumor Suppressor Proteins; D025801:Ubiquitin / Q000378:metabolism*; D044763:Ubiquitin-Conjugating Enzymes; D044767:Ubiquitin-Protein Ligases; D014709:Vero Cells
D034961:Antigens, Nuclear; D001324:Autoantigens; D017874:Immediate-Early Proteins; D033862:Iron-Binding Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D025801:Ubiquitin; C066642:SP100 protein, human; C070576:PML protein, human; C097308:UBE2D1 protein, human; D044763:Ubiquitin-Conjugating Enzymes; D044767:Ubiquitin-Protein Ligases; C051804:Vmw110 protein, Human herpesvirus 1; D008025:Ligases