دورية أكاديمية
Sp3 Transcription Factor Cooperates with the Kaposi's Sarcoma-Associated Herpesvirus ORF50 Protein To Synergistically Activate Specific Viral and Cellular Gene Promoters.
العنوان: | Sp3 Transcription Factor Cooperates with the Kaposi's Sarcoma-Associated Herpesvirus ORF50 Protein To Synergistically Activate Specific Viral and Cellular Gene Promoters. |
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المؤلفون: | Chen LY; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang-Gung University, Taoyuan, Taiwan., Chen LW; Department of Respiratory Care, Chang-Gung University of Science and Technology, Chiayi, Taiwan.; Department of Pediatric Surgery, Chang-Gung Memorial Hospital, Chiayi, Taiwan., Peng KT; Department of Orthopedic Surgery, Chang-Gung Memorial Hospital, Chiayi, Taiwan., Hung CH; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang-Gung University, Taoyuan, Taiwan., Chang PJ; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang-Gung University, Taoyuan, Taiwan peyjiumc@mail.cgu.edu.tw a483662@yahoo.com.tw.; Department of Nephrology, Chang-Gung Memorial Hospital, Chiayi, Taiwan., Wang SS; Department of Pediatric Surgery, Chang-Gung Memorial Hospital, Chiayi, Taiwan peyjiumc@mail.cgu.edu.tw a483662@yahoo.com.tw.; School of Medicine, Chang-Gung University, Taoyuan, Taiwan. |
المصدر: | Journal of virology [J Virol] 2020 Aug 31; Vol. 94 (18). Date of Electronic Publication: 2020 Aug 31 (Print Publication: 2020). |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: American Society For Microbiology Country of Publication: United States NLM ID: 0113724 Publication Model: Electronic-Print Cited Medium: Internet ISSN: 1098-5514 (Electronic) Linking ISSN: 0022538X NLM ISO Abbreviation: J Virol Subsets: MEDLINE |
أسماء مطبوعة: | Publication: Washington Dc : American Society For Microbiology Original Publication: Baltimore, American Society for Microbiology. |
مواضيع طبية MeSH: | Promoter Regions, Genetic* , Transcription, Genetic*, Herpesvirus 8, Human/*genetics , Immediate-Early Proteins/*genetics , Sp1 Transcription Factor/*genetics , Sp3 Transcription Factor/*genetics , Trans-Activators/*genetics, Animals ; Binding Sites ; Cell Line ; Cell Line, Tumor ; Clone Cells ; Fibroblasts/virology ; Gene Expression Regulation ; HEK293 Cells ; Herpesvirus 8, Human/metabolism ; Host-Pathogen Interactions/genetics ; Humans ; Immediate-Early Proteins/metabolism ; Immunoglobulin J Recombination Signal Sequence-Binding Protein/genetics ; Immunoglobulin J Recombination Signal Sequence-Binding Protein/metabolism ; Interleukin-10/genetics ; Interleukin-10/metabolism ; Lymphocytes/virology ; Mice ; Protein Binding ; Response Elements ; Signal Transduction ; Sp1 Transcription Factor/metabolism ; Sp3 Transcription Factor/metabolism ; Trans-Activators/metabolism ; Viral Proteins/genetics ; Viral Proteins/metabolism ; Viral Regulatory and Accessory Proteins/genetics ; Viral Regulatory and Accessory Proteins/metabolism |
مستخلص: | The Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded open reading frame 50 (ORF50) protein is the key transactivator responsible for the latent-to-lytic switch. Here, we investigated the transcriptional activation of the ORF56 gene (encoding a primase protein) by ORF50 and successfully identified an ORF50-responsive element located in the promoter region between positions -97 and -44 (designated 56p-RE). This 56p-RE element contains a noncanonical RBP-Jκ-binding sequence and a nonconsensus Sp1/Sp3-binding sequence. Electrophoretic mobility shift assays revealed that RBP-Jκ, Sp3, and ORF50 could form stable complexes on the 56p-RE element. Importantly, transient-reporter analysis showed that Sp3, but not RBP-Jκ or Sp1, acts in synergy with ORF50 to activate the 56p-RE-containing reporter construct, and the synergy mainly depends on the Sp1/Sp3-binding region of the 56p-RE element. Sequence similarity searches revealed that the promoters for ORF21 (thymidine kinase), ORF60 (ribonucleotide reductase, small subunit), and cellular interleukin-10 (IL-10) contain a sequence motif similar to the Sp1/Sp3-binding region of the 56p-RE element, and we found that these promoters could also be synergistically activated by ORF50 and Sp3 via the conserved motifs. Noteworthily, the conversion of the Sp1/Sp3-binding sequence of the 56p-RE element into a consensus high-affinity Sp-binding sequence completely lost the synergistic response to ORF50 and Sp3. Moreover, transcriptional synergy could not be detected through other ORF50-responsive elements from the viral PAN, K12, ORF57, and K6 promoters. Collectively, the results of our study demonstrate that ORF50 and Sp3 can act in synergy on the transcription of specific gene promoters, and we find a novel conserved cis -acting motif in these promoters essential for transcriptional synergy. IMPORTANCE Despite the critical role of ORF50 in the KSHV latent-to-lytic switch, the molecular mechanism by which ORF50 activates its downstream target genes, especially those that encode the viral DNA replication enzymes, is not yet fully understood. Here, we find that ORF50 can cooperate with Sp3 to synergistically activate promoters of the viral ORF56 (primase), ORF21 (thymidine kinase), and ORF60 (ribonucleotide reductase) genes via similar Sp1/Sp3-binding motifs. Additionally, the same synergistic effect can be seen on the promoter of the cellular IL-10 gene. Overall, our data reveal an important role for Sp3 in ORF50-mediated transactivation, and we propose a new subclass of ORF50-responsive elements in viral and cellular promoters. (Copyright © 2020 Chen et al.) |
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فهرسة مساهمة: | Keywords: IL-10; Kaposi’s sarcoma-associated herpesvirus; ORF21; ORF50; ORF56; ORF60; Sp3; synergistic activation |
المشرفين على المادة: | 0 (IL10 protein, human) 0 (Immediate-Early Proteins) 0 (Immunoglobulin J Recombination Signal Sequence-Binding Protein) 0 (ORF57 protein, human herpesvirus 8) 0 (RBPJ protein, human) 0 (Rta protein, Human herpesvirus 8) 0 (SP3 protein, human) 0 (Sp1 Transcription Factor) 0 (SP1 protein, human) 0 (Trans-Activators) 0 (Viral Proteins) 0 (Viral Regulatory and Accessory Proteins) 0 (kaposin B protein, Human herpesvirus 8) 130068-27-8 (Interleukin-10) 148710-94-5 (Sp3 Transcription Factor) |
تواريخ الأحداث: | Date Created: 20200710 Date Completed: 20201124 Latest Revision: 20231213 |
رمز التحديث: | 20231215 |
مُعرف محوري في PubMed: | PMC7459565 |
DOI: | 10.1128/JVI.01143-20 |
PMID: | 32641483 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1098-5514 |
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DOI: | 10.1128/JVI.01143-20 |