Large-scale identification and characterization of human genes that activate NF-kappaB and MAPK signaling pathways.
We have carried out a large-scale identification and characterization of human genes that activate the NF-kappaB 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-kappaB 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-kappaB binding sites. In total, we identified 299 cDNAs that activate the NF-kappaB pathway, and we classified them into 83 genes, including 30 characterized activator genes of the NF-kappaB pathway, 28 genes whose involvement in the NF-kappaB 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-kappaB and the MAPK pathways, which may indicate that these genes play cross-talking roles between these two pathways.
Matsuda
Akio
A
Laboratory for Biology, Institute for Life Science Research, Health Care Company, ASAH1 KASEI Corporation, 2-1 Samejima, Fuji-shi, Shizuoka 416-8501, Japan. matsuda.ab@om.asahi-kasei.co.jp
Suzuki
Yutaka
Y
Honda
Goichi
G
Muramatsu
Shuji
S
Matsuzaki
Osamu
O
Nagano
Yukiko
Y
Doi
Takahiro
T
Shimotohno
Kunitada
K
Harada
Takeshi
T
Nishida
Eisuke
E
Hayashi
Hiroshi
H
Sugano
Sumio
S
D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D018076:DNA, Complementary; D015723:Gene Library; D015894:Genome, Human; D006801:Humans; D020935:MAP Kinase Signaling System; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D016415:Sequence Alignment; D015398:Signal Transduction; D024363:Transcription Initiation Site; D015533:Transcriptional Activation
D018076:DNA, Complementary; D016328:NF-kappa B