Search results for CASP8

Showing 8 results out of 45

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Protein (4 results from a total of 16)

Identifier: R-HSA-3927945
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: CASP8AP2: Q9UKL3
Identifier: R-HSA-3927850
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: Q9UKL3
Identifier: R-HSA-3927863
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: P63165
Identifier: R-HSA-3465408
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: O15519-1

Reaction (4 results from a total of 18)

Identifier: R-HSA-5675456
Species: Homo sapiens
Compartment: cytosol, plasma membrane
The balance between caspase-dependent apoptosis and RIPK-dependent necroptosis was found to depend on the levels of caspase-8 (CASP8) and cellular FADD-like interleukin-1 beta converting enzyme (FLICE)-inhibitory protein (cFLIP, encoded by the CFLAR gene) (Feoktistova M et al. 2011; Hughes MA et al. 2016; reviewed in Tummers B & Green DR 2017). cFLIP exists in two main isoforms: long FLIP(L) and short FLIP(S) forms. Both FLIP(L) and FLIP(S) form heterodimers with procaspase-8, however they differentially regulate CASP8 activation (Feoktistova M et al. 2011; Dillon CP et al. 2012). The pseudoprotease FLIP(L) interacts with procaspase-8 through both death effector domains (DED) and caspase-like domain (CLD) that lacks catalytic activity due to absence of a cysteine residue in FLIP(L). The procaspase-8 catalytic domain prefers heterodimerization with the CLD of FLIP(L) over homodimerization with catalytic domains of other procaspase-8 molecules (Boatright KM et al. 2004; Yu JW et al. 2009). Heterodimerization to FLIP(L) rearranges the catalytic site of procaspase-8, producing a conformation that renders the heterodimer highly active even in the absence of proteolytic processing of either caspase-8 or cFLIPL (Micheau O et al. 2002; Yu JW et al. 2009; reviewed in Tummers B & Green DR 2017). The regulatory function of FLIP(L) has been found to differ depending on its expression levels. FLIP(L) was shown to inhibit death receptor (DR)-mediated apoptosis only when expressed at high levels, while low cell levels of FLIP(L) enhanced DR signaling to apoptosis (Boatright KM et al. 2004; Okano H et al. 2003; Yerbes R et al. 2011; Hughes MA et al. 2016). When FLIP(L) is expressed at high levels, the enzymatic activity of the FLIP(L):CASP8 heterodimer with procaspase-8 being an active unit is insufficient to generate active CASP8 heterotetramers for the apoptosis induction in mammalian cells. In contrary, the residual catalytic activity of FLIP(L):CASP8 is sufficient for RIPK1/RIPK3 cleavage, which inhibited the necroptotic cell death mode (Feoktistova M et al. 2011; Dillon CP et al. 2012; Oberst A et al. 2011).
Identifier: R-HSA-9697747
Species: Homo sapiens
Compartment: cytosol
The balance between caspase-dependent apoptosis and RIPK-dependent necroptosis was found to depend on the levels of FADD-like interleukin-1 beta converting enzyme (FLICE)-inhibitory protein isoforms (cFLIP, encoded by the CFLAR gene) (reviewed in Tummers B & Green DR 2017). cFLIP exists in two main isoforms: long FLIP(L) and short FLIP(S) forms. Both FLIP(L) and FLIP(S) dimerize with procaspase-8 at the death‑inducing signaling complex (DISC) such as TRADD:TRAF2:RIPK1: FADD:CASP8:FLIP(L), however they differentially regulate CASP8 activation (Pop C et al. 2011; Oberst A et al. 2011; Hughes MA et al. 2009, 2016). 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). Processing of FLIP(L) also occurs at the DISC and depends on CASP8 activity (zymogen and mature form). Upon activation FLIP(L) is cleaved to generate N‑terminal FLIP(p43) and C‑terminal FLIP(p12) (Irmler M et al. 1997; Chang DW et al. 2002; Yu JW et al. 2009; Pop C et al. 2011). FLIP(S) is a truncated version of procaspase‑8 containing tandem DEDs only. FLIP(S) acts purely as an antagonist of CASP8 activity inhibiting apoptosis. 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). Important to note that the latest statement has been shown in the context of the TLR3 signalling pathway.
Identifier: R-HSA-9603534
Species: Homo sapiens
Compartment: plasma membrane, cytosol
In the absence of ligand, NTRK3 (TRKC) is cleaved by an unknown caspase. CASP3 (caspase-3) cleaves NTRK3 in vitro, but CASP3 inhibitors do not prevent NTRK3 cleavage in live cells. CASP8 (caspase-8) is unable to cleave NTRK3 in vitro. A general caspase inhibitor prevents NTRK3 cleavage in live cells (Tauszig-Delamasure et al. 2007).
Identifier: R-HSA-5692550
Species: Homo sapiens
Compartment: cytosol
Human cytomegalovirus (HCMV) encodes several viral cell death inhibitors that target different key regulators of the extrinsic and intrinsic apoptotic pathways. Viral inhibitor of caspase-8 activation (vICA) protein encoded by the UL36 gene suppresses the extrinsic apoptotic signaling pathway by binding to the prodomain of caspase-8 (CASP8) and preventing its activation (Skaletskaya A et al. 2001; McCormick et al, 2010; Fliss PM & Brune W 2012).
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