Ymer Acts as a Multifunctional Regulator in Nuclear Factor-κB and Fas Signaling Pathways

Abstract

The nuclear factor (NF)-κB family of transcription factors regulates diverse cellular functions, including inflammation, oncogenesis and apoptosis. It was reported that A20 plays a critical role in the termination of NF-κB signaling after activation. Previously, we showed that Ymer interacts and collaborates with A20, followed by degradation of receptor-interacting protein (RIP) and attenuation of NF-κB signaling. Here we show the function of Ymer in regulation of several signaling pathways including NF-κB on the basis of results obtained by using Ymer transgenic (Ymer Tg) mice. Ymer Tg mice exhibited impaired immune responses, including NF-κB and mitogen-activated protein kinase (MAPK) activation, cell proliferation and cytokine production, to tumor necrosis factor (TNF)-α, polyI:C or lipopolysaccharide (LPS) stimulation. Ymer Tg mice were more resistant to LPS-induced septic shock than wild-type mice. Transgene of Ymer inhibited the onset of glomerulonephritis in lpr/lpr mice as an autoimmune disease model. In contrast to the inflammatory immune response to LPS, Fas-mediated cell death was strongly induced in liver cells of Ymer Tg mice in which Ymer is abundantly expressed. These findings suggest that Ymer acts as a regulator downstream of several receptors and that Ymer functions as a positive or negative regulator in a signaling pathway-dependent manner.

A Coiled‐Coil Domain Containing 50 Splice Variant Is Modulated by Serine/Arginine‐Rich Splicing Factor 3 and Promotes Hepatocellular Carcinoma in Mice by the Ras Signaling Pathway

“…CCDC50 is a multifunctional regulator of inflammation, cell death, and proliferation. CCDC50 is therefore presumed to be closely related to growth factor signaling or carcinogenesis . In researching the biological consequences of elevated CCDC50S expression in HCC, we provided multiple lines of evidence to demonstrate that CCDC50S accelerates proliferation and promotes migration of HCC cells in vitro and in vivo .…”

Transcriptome profiling reveals male- and female-specific gene expression pattern and novel gene candidates for the control of sex determination and gonad development in Xenopus laevis

“…Table 14 , and chosen genes are shown in Table 13 , and the functional groups are shown in Table 11 ). Among these upregulated genes are known genes such as epithelium markers keratin 5, 12, and 14, coiled-coil domain containing 50 ( ccdc50 ) that acts as an effector in EGF signaling and negative regulator of NF-kB factor (Tsukiyama et al 2012 ), signaling molecules: wnt3a, wnt7b, growth differentiation factor 3 ( gdf3 ), fibroblast growth factor–binding protein 1 ( fgfbp1 ), proteases cathepsin K and H, extracellular matrix molecules lumican, collagen IX and I, and decorin. A role of these genes in male sex determination and early testis development remains unknown.…”

Coiled-coil domain containing 50-V2 protein positively regulates neurite outgrowth

“…CCDC50 has been identified as a tyrosine-phosphorylated protein, and the tyrosine phosphorylation of CCDC50 inhibits the downregulation of EGFR [1][2][3] . CCDC50 is also involved in the regulation of RTK-mediated signalling pathways and acts as a multifunctional regulator of the large RTK family and various ligands 2,3,[26][27][28] ; CCDC50 is therefore presumed to be closely related to growth factor signalling. Here, we observed that CCDC50-V2 inhibits the EGFR signalling pathway by downregulating the EGFR level and suppressing the ERK and AKT signalling cascade via EGFR phosphorylation.…”