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Large-scale identification and characterization of human genes that activate NF-κB and MAPK signaling pathways

Oncogene volume 22, pages 3307–3318 (2003)Cite this article

Abstract

We have carried out a large-scale identification and characterization of human genes that activate the NF-κB and MARK signaling pathways. We constructed full-length cDNA libraries using the oligo-capping method and prepared an arrayed cDNA pool consisting of 150 000 cDNAs randomly isolated from the libraries. For analysis of the NF-κB signaling pathway, we introduced each of the cDNAs into human embryonic kidney 293 cells and examined whether it activated the transcription of a luciferase reporter gene driven by a promoter containing the consensus NF-κB binding sites. In total, we identified 299 cDNAs that activate the NF-κB pathway, and we classified them into 83 genes, including 30 characterized activator genes of the NF-κB pathway, 28 genes whose involvement in the NF-κB pathways have not been characterized and 25 novel genes. We then carried out a similar analysis for the identification of genes that activate the MARK pathway, utilizing the same cDNA resource. We assayed 145 000 cDNAs and identified 57 genes that activate the MARK pathway. Interestingly, 27 genes were overlapping between the NF-κB and the MAPK pathways, which may indicate that these genes play cross-talking roles between these two pathways.

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Acknowledgements

We thank K Ishizawa, M Yagi, T Sugahara, Nao Suzuki, S Suzuki, S Yoneta, Nori Suzuki and R Ooishi for their excellent screening and sequencing work. We are thankful to M Shirota and K Abe for their technical support and JM Sugano for helpful discussions. We are also grateful to E Nakajima for critical reading of the manuscript.

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Authors and Affiliations

  1. Laboratory for Biology, Institute for Life Science Research, Health Care Company, ASAH1 KASEI Corporation, 2-1 Samejima, Fuji-shi, Shizuoka, 416-8501, Japan

    Akio Matsuda, Goichi Honda, Shuji Muramatsu, Osamu Matsuzaki, Yukiko Nagano & Hiroshi Hayashi

  2. Laboratory of Genome Structure Analysis, Human Genome Center, Institute of Medical Science, the University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan

    Akio Matsuda, Yutaka Suzuki & Sumio Sugano

  3. Department of Viral Oncology, Institute for Virus Research, Kyoto University, 53 Kawara-cho Shogo-in, Sakyo-ku, Kyoto, 606-8507, Japan

    Takahiro Doi & Kunitada Shimotohno

  4. Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto, 606-8502, Japan

    Takeshi Harada & Eisuke Nishida

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  1. Akio Matsuda
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  2. Yutaka Suzuki
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Correspondence to Akio Matsuda.

Additional information

The nucleotide sequences reported in this paper have been deposited in the DDBJ, EMBL and Genbank database under the Accession numbers AB97000–AB97053

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Matsuda, A., Suzuki, Y., Honda, G. et al. Large-scale identification and characterization of human genes that activate NF-κB and MAPK signaling pathways. Oncogene 22, 3307–3318 (2003). https://doi.org/10.1038/sj.onc.1206406

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