Herpes virus proteins ICP0 and BICP0 can activate NF-kappaB by catalyzing IkappaBalpha ubiquitination.
The immediate early proteins ICP0 and BICP0 from Herpes virus are promiscuous activators of both viral and cellular genes and play a critical role in virus life cycle. Here we report that ICP0 and BICP0 could induce NF-kappaB translocation from cytoplasm into nucleus and strongly activate NF-kappaB responsive genes specifically. This process was dependent on the RING domain of both proteins. In addition, ICP0 interacted specifically with IkappaBalpha and its activating effect was attenuated by Ubch5A(C85A) and MG132, but not by IkappaBalpha(S32A/S36A). Remarkably, IkappaBalpha was poly-ubiquitinated by both ICP0 and BICP0, in vitro and in vivo. These data indicate that ICP0 and BICP0, functioning as ubiquitin ligases, are bona fide activators of NF-kappaB signaling pathway. Our study identifies a new way ICP0 and BICP0 explore to regulate gene expression.
Diao
Lirong
L
Laboratory of Molecular and Cellular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Box 49, 320 Yue Yang Road, Shanghai 200031, P.R. China.
Zhang
Bianhong
B
Fan
Junkai
J
Gao
Xiang
X
Sun
Shaogang
S
Yang
Kai
K
Xin
Dan
D
Jin
Naihe
N
Geng
Yunqi
Y
Wang
Chen
C
D000818:Animals; D002417:Cattle; D002460:Cell Line; D045744:Cell Line, Tumor; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D024202:Electrophoretic Mobility Shift Assay; D015967:Gene Expression Regulation, Viral; D006801:Humans; D051550:I-kappa B Kinase; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism*; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D033862:Iron-Binding Proteins / Q000235:genetics / Q000378:metabolism; D007976:Leupeptins / Q000494:pharmacology; D009154:Mutation; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D018139:Simplexvirus; D020079:Terminal Repeat Sequences / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051996:Transcription Factor RelA; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics; D014162:Transfection; D025801:Ubiquitin / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D015853:Cysteine Proteinase Inhibitors; D020672:I-kappa B Proteins; D017874:Immediate-Early Proteins; D033862:Iron-Binding Proteins; D007976:Leupeptins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D015534:Trans-Activators; D051996:Transcription Factor RelA; D025801:Ubiquitin; D014764:Viral Proteins; D000072000:NF-KappaB Inhibitor alpha; C097308:UBE2D1 protein, human; D044763:Ubiquitin-Conjugating Enzymes; D044767:Ubiquitin-Protein Ligases; C051804:Vmw110 protein, Human herpesvirus 1; C086729:bICP0 protein, Bovine herpesvirus 1; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde