Target of methylation-induced silencing (TMS1)/Apoptosis-associated speck-like protein containing a CARD (ASC), also referred to as PYCARD and CARD5, is a 22-kDa pro-apoptotic protein containing an N-terminal pyrin domain (PYD) and a C-terminal caspase recruitment domain (CARD). The ASC/TMS1 gene was originally found to be aberrantly methylated and silenced in breast cancer cells, and has since been found to be silenced in a number of other cancers, including ovarian cancer, glioblastoma, melanoma, gastric cancer, lung cancer, and prostate cancer. Expression of ASC/TMS1 can be induced by pro-apoptotic/inflammatory stimuli. During apoptosis ASC/TMS1 is re-distributed from the cytosol to the mitochondria and associates with mitochondrial Bax to trigger cytochrome c release and subsequent apoptosis. ASC/TMS1 has also been found to be a critical component of inflammatory signaling where it associates with and activates caspase-1 in response to pro-inflammatory signals.
TNF-α is secreted by macrophages, monocytes, neutrophils, T-cells, and NK-cells. Many transformed cell lines also secrete TNF-α. Monomeric mouse TNF-α is 156 amino acid protein (N-glycosylated) with a reported molecular weight of 17.5 kD protein. TNF-α forms multimeric complexes; stable trimers are most common in solution. A 26 kD membrane form of TNF-α has also been described. TNF-α binding to surface receptors elicits a wide array of biologic activities including: cytolysis and cytostasis of many tumor cell lines in vitro, hemorraghic necrosis of tumors in vivo, increased fibroblast proliferation, and enhanced chemotaxis and phagocytosis in neutrophils.
TNF RI occurs both in membrane bound and soluble forms and functions as a receptor for TNF-alpha and TNF-beta. In the superfamily nomenclature, it is designated TNFRSF1A.
TNF receptor II (TNF-R2) is one of the receptors of TNF-α. The two receptors for TNF-α, TNF-R1 (55 kDa) and TNF-R2 (75 kDa), can mediate distinct cellular responses. In most cases, cytotoxicity elicited by TNF has been reported to act through TNF-R1. In contrast, TNF-R2 appears to be important in T cell signaling and responses to infection. TNF-R2 binds to distinct members of the TRAF family, leading to the activation of NF-κB. Soluble forms of both receptors have also been characterized which can bind TNF-α and may play an important role in immune disorders.
This gene encodes a multifunctional proinflammatory cytokine that belongs to the tumor necrosis factor (TNF) superfamily. This cytokine is mainly secreted by macrophages. It can bind to, and thus functions through its receptors TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. This cytokine is involved in the regulation of a wide spectrum of biological processes including cell proliferation, differentiation, apoptosis, lipid metabolism, and coagulation. This cytokine has been implicated in a variety of diseases, including autoimmune diseases, insulin resistance, and cancer. Knockout studies in mice also suggested the neuroprotective function of this cytokine.
TOMM20 (Translocase Of Outer Mitochondrial Membrane 20) is a Protein Coding gene. Diseases associated with TOMM20 include Perry Syndrome and Infantile Neuroaxonal Dystrophy 1. Among its related pathways are Deubiquitination and Neuroscience. GO annotations related to this gene include unfolded protein binding and P-P-bond-hydrolysis-driven protein transmembrane transporter activity. An important paralog of this gene is TOMM20L.
Central component of the receptor complex responsible for the recognition and translocation of cytosolically synthesized mitochondrial preproteins. Together with tom22 functions as the transit peptide receptor at the surface of the mitochondrion outer membrane and facilitates the movement of preproteins into the tom40 translocation pore.,similarity:Belongs to the Tom20 family.,subunit:Forms part of the preprotein translocase complex of the outer mitochondrial membrane (TOM complex) which consists of at least 7 different proteins (TOMM5, TOMM6, TOMM7, TOMM20, TOMM22, TOMM40 and TOMM70). Interacts with TOM22.
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