Inhibitor of Apoptosis Proteins: a family of proteins with antiapoptotic effect, probably by inhibiting Caspase-3 and -7. IAP-dependent inhibition of caspase activity is essential for cell survival, and one mechanism for cell death activation involves inhibition of IAP function (Wang et al., 1999, Cell, 98: 453-463; Goyal et al., 2000, EMBO, 19: 589-597). For reviews see Deveraux and Reed, 1999, Genes Dev., 13: 239-252 and Miller, 1999, Trends Cell Biol., 9: 323-328. More
Inhibitor of CAD (Caspase-activated DNase), identified in mouse cells, ICAD is homologous to human DFF45. ICAD binds to CAD, and inhibits its DNase activity. Active Caspase-3 cleaves ICAD and by this activates CAD what results in oligonucleosomal DNA cleavage. ICAD is not just inhibitor of CAD but probably also chaperone for CAD, since active CAD is only expressed in presence of ICAD. For a review see Nagata, 2000, Exp. Cell Res. 256: 12-18.
Interferon-gamma; cytokine with antiviral effect produced by cytotoxic CD8+ T lymphocytes and CD4+ Th1 cells but not by Th2 lymphocytes. It inhibits proliferation of T2h cells, activates macrophage functions and regulates antibody production of B lymphocytes.
Insulin-like Growth Factor-Binding Protein 3 (IGF-BP3) is a target gene of p53 and is able to inhibit mitogenic signalling by the insulin-like growth factor IGF-1. IGF-BP3 may link p53 to as yet uncharacterized autocrine/paracrine signalling pathways.
IKK-complex-Associated Protein is a scaffold component of the heigh molecular weight IKK complexes. Like NEMO/IKK-gamma, IKAP binds to IKKs directly, but it also binds to NIK. It might direct the assembly or disassembly of IKK complexes in response to signalling, and control deactivation of the kinase complex after stimulation.
IkB-proteins (IkB-alpha, beta, and epsilon) are inhibitor proteins of NF-kB, which keep cytosolic NF-kB under tight control by binding to NF-kB and blocking its transport into the nucleus. For NF-kB activation, IkB-alpha is phosphorylated by IKKs at two serine residues what results in the binding of ubiquitin to and degradation of IkB-alpha by the proteasome.
Two IkB kinases (IKKs) have been cloned : IKK-alpha and -beta. They are the only kinases known to phosphorylate IkB-alpha at the same residues that are modified in response to agents that activate NF-kB. IKKs are part of multi-protein complexes (800 kDa) which include the IKK-alpha and -beta, NEMO/IKK-gamma, IKAP and NIK.
Immune system and Apoptosis
Apoptosis plays an important role in shaping the repertoire of lymphocytes and in regulating the size of the mature lymphocyte pool. In the T cell pool, nonfunctional cells as well as self-reactive cells are eliminated by apoptosis. The best-defined regulators of apoptosis in cells of the immune system are Fas and members of the Bcl-2 family. Fas (CD95) induces apoptosis in activated T cells at the end of an immune response (AICD). Fas also functions to maintain T cell tolerance by deleting autoreactive cells and constitutes an important pathway of killing for cytotoxic T cells. The Bcl-2 family proteins, particularly Bcl-2 and Bcl-xL, prevent T cells from undergoing apoptosis in response to various stimuli. Apoptosis or defects in apoptosis are involved in immunological diseases such as the autoimmune disease ALPS, B cell lymphoma, and AIDS. More
The immunoglobulin fold is one of the most versatile and widely-used structural units of proteins. The immunoglobulin fold was originally characterized as the globular modules that form the homology domains of immunoglobulins. Its secondary structure consists of a barrel that is composed of a three- and a four-stranded antiparallel beta-sheet which are linked by a disulfide bond.
Invasiveness of tumor cells implies an ability to break loose, enter the blood stream or lymphatic vessels, and form secondary tumors (metastases) at other sites in the body.
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