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

Abstract

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.

Genome-Wide Identification of Novel Genes Involved in Early Th1 and Th2 Cell Differentiation

“…Also, the exact mechanism of this enhancement remains to be elucidated. One of the possible mechanisms may involve the NF-B pathway, as NDFIP2 has been suggested to activate NF-B signaling (40). Alternatively, NDFIP2 may regulate cytokine production through some novel mechanism related to protein trafficking.…”

A homologue of the Drosophila headcase protein is a novel tumor marker for early-stage colorectal cancer

“…However, the significance of the altered HECA levels is not clearly understood, nor is it clear whether these increases are a cause or consequence of colorectal cancer. In addition, other than HECA, genes for sulfide dehydrogenase-like (34), coiled-coil and C2 domain containing 1A (CC2D1A) that can activate the NF-κB and MAPK signaling pathway (35) and the hypothetical proteins, MGC10814 (36) and FLJ22662 (36), were also upregulated and detected in feces. For the purpose of molecular staging and screening in a noninvasive manner, the data for HECA support further evaluation of other novel candidates.…”

The role of BST‐2/Tetherin in host protection and disease manifestation

“…We posit that BST‐2‐mediated cell‐to‐cell adhesion (that mimics BST‐2‐mediated virus tethering) is the mechanism of NF‐κB activation. BST‐2‐mediated activation of NF‐κB 14, 15, 16, 17 may result in the induction of several factors involved in cancer cell migration and invasion including matrix metalloproteases, chemokines, or growth factors (Fig. 3, Box 2), as well as in intravasation of tumor cells (Fig.…”

“…The C‐terminal membrane anchor is thought to be a second TM domain rather than a GPI anchor 12. The cytoplasmic tail of BST‐2 contains a highly conserved double tyrosine motif (6 Y 7 × 8 Y ) implicated in clathrin‐dependent endocytosis of BST‐2 13 and in nuclear factor κ‐B (NF‐κB) activation 14, 15, 16, 17 (Fig. 1).…”