Also acts as a regulator of innate immunity by mediating cleavage and inactivation of N4BP1 downstream of TLR3 or TLR4, thereby promoting cytokine production (By similarity). Initiates pyroptosis following inactivation of MAP3K7/TAK1 (By similarity). Also able to initiate pyroptosis by mediating cleavage and activation of gasdermin-D (GSDMD): GSDMD cleavage promoting release of the N-terminal moiety (Gasdermin-D, N-terminal) that binds to membranes and forms pores, triggering pyroptosis (By similarity). In addition to extrinsic apoptosis, also acts as a negative regulator of necroptosis: acts by cleaving RIPK1 at 'Asp-324', which is crucial to inhibit RIPK1 kinase activity, limiting TNF-induced apoptosis, necroptosis and inflammatory response (PubMed: 31827280, PubMed: 31827281). Proteolytic fragments of the N-terminal propeptide (termed CAP3, CAP5 and CAP6) are likely retained in the DISC (PubMed: 9184224).
TRAF PROTEIN SCAFFOLD FREE
The active dimeric enzyme is then liberated from the DISC and free to activate downstream apoptotic proteases (PubMed: 9184224). The resulting aggregate called death-inducing signaling complex (DISC) performs CASP8 proteolytic activation (PubMed: 9184224). Binding to the adapter molecule FADD recruits it to either receptor TNFRSF6/FAS mediated or TNFRSF1A (PubMed: 8681376, PubMed: 8681377). Cleaves and activates effector caspases CASP3, CASP4, CASP6, CASP7, CASP9 and CASP10 (PubMed: 8962078, PubMed: 9006941). Initiator protease that induces extrinsic apoptosis by mediating cleavage and activation of effector caspases responsible for the TNFRSF6/FAS mediated and TNFRSF1A induced cell death (PubMed: 23516580, PubMed: 8681376, PubMed: 8681377, PubMed: 9006941, PubMed: 9184224, PubMed: 8962078). Thiol protease that plays a key role in programmed cell death by acting as a molecular switch for apoptosis, necroptosis and pyroptosis, and is required to prevent tissue damage during embryonic development and adulthood (By similarity). Many alternatively spliced transcript variants encoding different isoforms have been described, although not all variants have had their full-length sequences determined. This protein was detected in the insoluble fraction of the affected brain region from Huntington disease patients but not in those from normal controls, which implicated the role in neurodegenerative diseases. The N-terminal FADD-like death effector domain of this protein suggests that it may interact with Fas-interacting protein FADD. This protein is involved in the programmed cell death induced by Fas and various apoptotic stimuli. Activation of caspases requires proteolytic processing at conserved internal aspartic residues to generate a heterodimeric enzyme consisting of the large and small subunits. Caspases exist as inactive proenzymes composed of a prodomain, a large protease subunit, and a small protease subunit. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. This gene encodes a member of the cysteine-aspartic acid protease (caspase) family.
0 kommentar(er)
