Search results for CASP8

Showing 8 results out of 58

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Protein (4 results from a total of 17)

Identifier: R-HSA-351869
Species: Homo sapiens
Compartment: mitochondrial outer membrane
Primary external reference: UniProt: CASP8: Q14790
Identifier: R-HSA-933460
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: CASP8: Q14790
Identifier: R-HSA-76158
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: CASP8: Q14790
Identifier: R-HSA-351828
Species: Homo sapiens
Compartment: mitochondrial outer membrane
Primary external reference: UniProt: CASP8: Q14790

Reaction (4 results from a total of 31)

Identifier: R-HSA-9687458
Species: Homo sapiens
Compartment: cytosol
During infection in human cells, herpes simplex virus 1 (HSV1) and HSV2 modulate cell death pathways using the large subunit (R1) of viral ribonucleotide reductase (RIR1 or UL39) proteins (Dufour F et al. 2011; Guo H et al. 2015; Yu X et al. 2016; Ali M et al. 2019). The HSV1 and HSV2 RIR1 proteins suppress death receptor-dependent apoptosis by interacting with death effector domains of caspase 8 (CASP8) via a conserved C-terminal ribonucleotide reductase (RNR) domain (Dufour F et al. 2011). The ability of HSV1 RIR1 and HSV2 RIR1 to bind CASP8 is integral to their suppression activity against necroptosis in human cells. Necroptosis complements apoptosis as a host defense pathway to stop virus infection and is mediated by the interaction between receptor‐interacting protein kinase 1 (RIPK1) and RIPK3 that occurs downstream of tumor necrosis factor receptor 1 (TNFR1) activation during the programmed cell death response (Sun X et al. 2002). The N-terminal region of HSV1 and HSV2 RIR1 proteins carrying the RIP homotypic interaction motif (RHIM)-like element is sufficient for RHIM-dependent interaction with RIPK1 and RIPK3 thus inhibiting the interaction between RIPK1 and RIPK3 (Guo H et al. 2015; Yu X et al. 2015). HSV1 RIR1 and HSV2 RIR1 are thought to block the programmed cell death responses in infected human cells by interactions with RIPK1, RIPK3 and CASP8 (Guo H et al. 2015; Mocarski ES et al. 2015).
Identifier: R-HSA-9757951
Species: Homo sapiens
Compartment: cytosol
NEDD4-binding protein 1 (N4BP1) limits the activation of NF-kappaB downstream of TICAM1 (TRIF)-independent Toll-like receptor 2 (TLR2), TLR7 or TLR9 signaling pathways, but not upon engagement of TLR3 or TLR4 which utilize the adaptor protein TICAM1 (Shi H et al. 2021; Gitlin AD et al. 2020). TLR3- or TRL4-induced TICAM1-dependent activation of caspase-8 (CASP8) was found to inactivate N4BP1 via the proteolytic cleavage thus promoting NF-kappa-B activation (Gitlin AD et al. 2020; Shi H et al. 2021). Functional studies of N4BP1 mutants expressed in human embryonic kidney 293T (HEK293T) cells suggest that human N4BP1 is cleaved after D424 and/or D490 (Shi H et al. 2021).
Identifier: R-HSA-9697750
Species: Homo sapiens
Compartment: cytosol
Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) can be a part of cell death and survival signaling complexes. Whether RIPK1 functions in apoptosis, necroptosis or NFkB signaling is dependent on autocrine/paracrine signals, on the cellular context and tightly regulated by posttranslational modifications of RIP1 itself. Following ligation of TNFR1, RIPK1 is recruited to the TNFR1:TRADD:TRAF2 complex where it is ubiquitinated by BIRC2/3 (also known as inhibitor of apoptosis proteins cIAP1/2) and LUBAC. Polyubiquitination of RIPK1 is required for recruitment of signaling molecules/complexes such as the IKK complex and TAK1 complex. IKKs and TAK1 phosphorylate RIPK1 to limit its cytotoxic activity and activate NFkappaB and MAPK pathways, resulting in expression of both pro-inflammatory cytokines and pro-survival genes including FADD-like interleukin-1 beta converting enzyme (FLICE)-inhibitory protein (cFLIP, encoded by the CFLAR gene) (Ea CK et al. 2006). Conversely, deubiquitination of RIPK1, mediated by BIRC2/3 (cIAP) inhibition or the deubiquitylases A20 or CYLD, switches the pro-survival function of RIPK1 to caspase-mediated pro-apoptotic signaling (Fujikura D et al. 2012; Moquin DM et al. 2013). The TRADD:TRAF2:RIPK1 complex detaches from TNFR1 and recruits FADD and procaspase-8 (CASP8). CASP8 in human and rodent cells facilitates the cleavage of kinases RIPK1 and RIPK3 and prevents RIPK1/RIPK3-dependent necroptosis (Lin Y et al. 1999; Hopkins-Donaldson S et al. 2000; Meng H et al. 2018; Newton K et al. 2019; Zhang X et al. 2019; Tao P et al. 2020; Lalaoui N et al. 2020). The balance between caspase-dependent apoptosis and RIPK-dependent necroptosis was found to depend on the levels of CASP8 and cFLIP (CFLAR) (reviewed in Tummers B & Green DR 2017). In the presence of cFLIP, both CASP8 and FLIP are recruited to the TRADD:TRAF2:RIPK1:FADD complex. cFLIP exists in two main isoforms: long FLIP(L) and short FLIP(S) forms. The heterodimers of FLIP(L):CASP8 inhibit CASP8 activity limiting the cleavage of CASP3/7 but allowing the cleavage of RIPK1 to cause the dissociation of the TRADD:TRAF2:RIPK1:FADD:CASP8 complex, thereby inhibiting both apoptosis and necroptosis (Pop C et al. 2011; Oberst A et al. 2011; Hughes MA et al. 2009; Lalaoui N et al 2020). FLIP(S) has also been proposed to induce necroptosis in conditions when RIPK1 is deubiquitylated and when FLIP(L) is absent (Feoktistova M et al. 2011). Note that the latest statement has been proven in the context of the TLR3 signalling pathway.
Identifier: R-HSA-5228521
Species: Homo sapiens
Compartment: nucleoplasm
PIAS1, PIAS4 SUMOylate CASP8AP2 (FLASH) at lysine-1813 with SUMO1 (Alm-Kristiansen et al. 2009, Alm-Kristiansen et al. 2011). SUMOylation enhances the transcriptional coactivation activity of CASP8AP2. As inferred from mouse homologs, SUMOylation also appears to trigger proteasomal degradation of CASP8AP2 (Vennemann and Hofmann 2013).
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