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KMID : 0578320110320060555
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Molecules and Cells
2011 Volume.32 No. 6 p.555 ~ p.560
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Nuclear Factor-κB2 Represses Sp1-Mediated Transcription at the CD99 Promoter
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Lee Eun-Kyung
Chae Ji-Hye
Kang Myung-Soo
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Abstract
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Downregulation of the CD99 antigen on the surface of Hodgkin’s lymphoma (HL) cells via EBV LMP1-mediated NF-?B suppression of Sp1 transcriptional activity is known to be associated with the appearance of pathogenic Reed-Sternberg cells. Here, we show that in addition to EBV LMP1 heterologous NF-?B activators such as CD30 and CD40 repress the CD99 promoter, which contains multiple Sp1-binding sites but no NF-?B binding sites. In addition, NF-?B-inducing kinase (NIK) repressed the CD99 promoter while NIK kinase mutants and JNK inhibitory protein failed to do so. Of the NF-?B subunits, NF-?B2 (p52) alone or in combination with other Rel subunits consistently inhibited the CD99, while NF-?B1 (p50) showed a marginal repressive effect. Furthermore, while transfection of LMP1 repressed the CD99 promoter in wild-type or NF-?B1 deficient MEFs, the same repression was not observed in NF-?B2 (p52)-deficient MEFs, indicating that NF-?B2 (p52) is required for LMP1-mediated repression of the CD99 promoter. Consistently, basal activity of the CD99 promoter was significantly higher in IKK?-/- and IKK?-/- MEFs, but not in IKK?-/- 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-medaited NF-?B2 exhibits the major inhibitory role in the transcription at the CD99 promoter.
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KEYWORD
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CD99, Hodgkin’s lymphoma, LMP1, P52, Sp1
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