title: Nuclear factor-κB2 represses Sp1-mediated transcription at the CD99 promoter.
abstract: Downregulation of the CD99 antigen on the surface of Hodgkin's lymphoma (HL) cells via EBV LMP1-mediated NF-κB suppression of Sp1 transcriptional activity is known to be associated with the appearance of pathogenic Reed-Sternberg cells. Here, we show that in addition, EBV LMP1 heterologous NF-κB activators such as CD30 and CD40 repress the CD99 promoter, which contains multiple Sp1-binding sites but no NF-κB binding sites. In addition, NF-κB-inducing kinase (NIK) repressed the CD99 promoter while NIK kinase mutants and JNK inhibitory protein failed to do so. Of the NF-κB subunits, NF-κB2 (p52) alone or in combination with other Rel subunits consistently inhibited the CD99, while NF-κB1 (p50) showed a marginal repressive effect. Furthermore, while transfection of LMP1 repressed the CD99 promoter in wild-type or NF-κB1 deficient MEFs, the same repression was not observed in NF-κB2 (p52)-deficient MEFs, indicating that NF-κB2 (p52) is required for LMP1-mediated repression of the CD99 promoter. Consistently, basal activity of the CD99 promoter was significantly higher in IKKα(-/-) and IKKβ(-/-) MEFs, but not in IKKΓ(-/-) MEFs compared to the wild-type control MEFs. Sp1-binding sites were directly used in the repression, because a synthetic Sp1 reporter with 10 Sp1-binding sites from the CD99 promoter was repressed by LMP1 or p52 transfection. These data indicate that LMP1-mediated NF-κB2 exhibits the major inhibitory role in the transcription at the CD99 promoter.
authors.affiliation: Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Korea.
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Lee
authors.forename: Ji Hye
authors.initials: JH
authors.lastname: Chae
authors.forename: Myung-Soo
authors.initials: MS
authors.lastname: Kang
mesh_terms: D000071443:12E7 Antigen; D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D019013:CD40 Antigens / Q000096:biosynthesis; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D057809:HEK293 Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D017730:Ki-1 Antigen / Q000096:biosynthesis; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D052003:NF-kappa B p52 Subunit / Q000378:metabolism / Q000502:physiology*; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D014158:Transcription, Genetic; D014763:Viral Matrix Proteins / Q000096:biosynthesis; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D000071443:12E7 Antigen; D015703:Antigens, CD; D019013:CD40 Antigens; D015815:Cell Adhesion Molecules; D048031:JNK Mitogen-Activated Protein Kinases; D017730:Ki-1 Antigen; D008156:Luciferases; D052003:NF-kappa B p52 Subunit; D017346:Protein Serine-Threonine Kinases; D011993:Recombinant Fusion Proteins; D016329:Sp1 Transcription Factor; D014763:Viral Matrix Proteins; D000097782:NF-kappaB-Inducing Kinase; C061828:CD99 protein, human; C037662:EBV-associated membrane antigen, Epstein-Barr virus; C498206:NFKB2 protein, human
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