Background
TNF is a multifunctional proinflammatory cytokine that belongs to the tumor necrosis factor (TNF) superfamily. This cytokine is mainly secreted by macrophages. TNF can bind to, and thus functions through its receptors TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. TNF is involved in the regulation of a wide spectrum of biological processes including cell proliferation, differentiation, apoptosis, lipid metabolism, and coagulation. TNF 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.
Alternative Names
Tumor Necrosis Factor, Tumor Necrosis Factor Ligand Superfamily Member 2, Cachectin, TNF-Alpha, TNFSF2, TNF-A, TNFA, Tumor Necrosis Factor (TNF Superfamily, Member 2), Tumor Necrosis Factor Ligand 1F
Cellular Localization
Plasma membrane, Extracellular region or secreted Cytosol
Involvement in Disease
Its related pathways are Apoptosis Modulation and Signaling and Monoamine Transport.
Related Pathways
1.Cytokines that bind to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can cause cell death in certain tumor cell lines. It is a strong pyrogen that directly acts or stimulates the secretion of interleukin-1 to cause fever. It is related to the induction of cachexia and can stimulate cell proliferation and induce cell differentiation under certain conditions. Dephosphorylation of FOXP3 impairs the function of regulatory T cells (Treg) in rheumatoid arthritis individuals. Up-regulating the expression of protein phosphatase 1 (PP1), PP1 dephosphorylates the key Ser-418 residue of FOXP3, thereby inactivating FOXP3 and deficient in Treg cell function (PubMed:23396208). In the RT4v6 bladder cancer cell line, bcg-stimulated neutrophils combined with DIABLO/SMAC mimics are key mediators of cell death in the anticancer effect (PubMed:22517918, PubMed:16829952, PubMed:23396208). By inhibiting insulin-induced IRS1 tyrosine phosphorylation and insulin-induced glucose uptake, it induces insulin resistance in adipocytes. Induces the degradation of GKAP42 protein in adipocytes, which is partly involved in tnf-induced insulin resistance (similar). 2. The formation of TNF intracellular domain (ICD) can induce dendritic cells to produce IL12.
Function
Cancer antibody; Cell Biology and Cellular Response antibody; Immune System antibody; Metabolism antibody; Signaling Transduction antibody
Field of research
1.The soluble form derives from the membrane form by proteolytic processing. The membrane-bound form is further proteolytically processed by SPPL2A or SPPL2B through regulated intramembrane proteolysis producing TNF intracellular domains (ICD1 and ICD2) released in the cytosol and TNF C-domain 1 and C-domain 2 secreted into the extracellular space. 2.The membrane form, but not the soluble form, is phosphorylated on serine residues. Dephosphorylation of the membrane form occurs by binding to soluble TNFRSF1A/TNFR1. 3.O-glycosylated; glycans contain galactose, N-acetylgalactosamine and N-acetylneuraminic acid.
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Antibody Clone
Ustekinumab
Description
Ustekinumab, a trademark of Stellara, is a human monoclonal antibody used to treat psoriasis. It was first approved for psoriasis and active psoriatic arthritis since 2009. It is made in the Netherlands. It is an antagonist that targets subcutaneous human interleukin 12 and interleukin 23, which are natural proteins that regulate the immune system and immune-mediated inflammatory diseases.
Indication
Psoriatic arthritis aggravated
Severe Plaque psoriasis
Ulcerative Colitis, Active Moderate
Ulcerative Colitis, Active Severe
Moderate Plaque psoriasis
Moderate, active Crohn´s Disease
Severe, active Crohn´s Disease