Caspases caspase recruitment domain

Activation of the caspases requires the help of a number of cofactors that are also known as activators or adaptors. Different cofactors are involved depending on the trigger mechanism of caspase activation. A central function of the cofactors is to bring about aggregation and thus activation of the procaspases. This occurs by specific protein-protein interactions with the help of common structural motives. Examples of such motives are the death domains (DD), death effector domains (DED) and the caspase recruitment domains (CARD), which all have a similar structure of six a-heh-ces. 

Caspase family. This scheme illustrates the domain structures, internal cleavage sites, preferred peptide substrate sequences, and biological function of caspases. Each procaspase consists of a large and small domain and may also possess DED (death effector domain) and CARD (caspase recruitment domain) (adapted from Hill etai, 2003). 

Fig. 5. The execution phase of apoptosis. An apoptotic stimulus causes the release of cytochrome c from mitochondria. The first box contains the components required to activate caspase 9 card refers to the caspase-recruitment domain. Caspase 9 then activates caspase 3 (second box), which in turn activates caspase 6 (last box). The amino-acid sequences at the cleavage sites are shown. Caspases 3 and 6 also have a prodomain that is not present in the active protease in caspase 6 an additional cleavage removes a small portion of the middle of the protein. Various substrates of the caspases are shown, including the pathway by which caspase-activated deoxyribonuclease (CAD) is activated which in turn leads to DNA...

The large prodomains of procaspases contain structural motifs that belong to the death domain (DD) superfamily involved in the transduction of the apoptotic signals. This superfamily consists of the DD, the death effector domain (DED), and the caspase recruitment domain (CARD). Each of these motifs interacts with other proteins by homotypic interactions. DED is found in procaspase-8 and -10, and CARD is found in procaspase-1, -2, -4, -5, -9, -11, and -12. DED and CARD are responsible for the recruitment of initiator caspases into death- or inflammation-inducing signaling complexes, resulting in proteolytic autoactivation of caspases that subsequently initiates inflammation and apoptosis [26, 29, 30],... 

Structural studies have revealed that several other domains involved in cell death and inflammatory signaling transduction, including the death effector domain (DED) (Fig. 11C), the caspase recruitment domain (CARD) and the Pyrin domain (PYD), also possess the same six helix bundle structures of DDs (Chou et al, 1998 Eberstadt et al, 1998 Hiller et al, 2003), forming the death domain superfamily. Interestingly, interactions have only been observed among proteins within the same subfamilies with no cross interactions between proteins from different subfamilies. 

Apoptosis repressor with caspase recruitment domain (ARC) 1 Engidawork et al. 2001c... 

Initiator caspases involved in the apoptotic process. These caspases, also known as apical caspases, are structurally characterized by the presence of a long prodomain at the N-terminal region containing different protein-protein interaction motifs such as death effector domain (DED) found in caspase-8 and-10 or caspase recruitment domain (CARD), present in caspase-2 and -9. Via... 

Caspase recruitment domain, mediates the formation of larger protein complexes via direct interactions between individual cards, involved in the regulation of caspase activation and apoptosis... 

Mutations in the NOD2/caspase recruitment domain 15 (CARD 15) and in the Toll-like receptor 4 (TLR4) gene are associated with an increased susceptibility for Crohn s disease (Leshinsky-Silver et al., 2005). 

Leshinsky-Silver E, Karban A, Buzhaker E, Fridlande M, Yakir B, Eliakim R, Reif S, Shaul R, Boaz M, Levi D, Levine A (2005) Is age of onset of Crohn s disease governed by mutation in NOD2/ caspase recruitment domain 15 and Toll-like receptor 4 Pediatr Res 58(3) 499-504. 

An alternative pathway involves the adaptor protein RAIDD (RIP-associated ICH/CED-3-homologous protein with a death domain), which is recruited by the Fas receptor via its C-terminal DD. At its N-terminus RAIDD contains a caspase recruitment domain (CARD) that is also present in procaspase-2. The adaptor protein TRADD (TNFR-associated death domain), most effectively bound following ligation of TNFR-1, functions as a platform that recruits several signalling molecules, such as TRAF-2 (the TNFR-associated factor-2), RIP (the receptor-interacting protein), both of which stimulate activation of NF-kB (the nuclear factor k B) and also FADD, which mediates activation of apoptosis (Ashkenazi and Dixit, 1998). TRAMP has been reported to bind TRADD, TRAF-2, FADD and caspase-8. TRAIL can bind either to a TRAIL-Rl trimer or to a TRAIL-R2 trimer, which recruit FADD and caspase-8 or caspase-10 (Schneider et al., 1997). 

Novel pathways include apoptotic protease-activating factor-1 (APAF-1) with an N-terminal caspase recruitment domain (CARD) recruiting caspase-9, or the RIP-like kinase CARDIAK specifically interacting with the CARD of caspase-1 (Thome et al., 1998). The overall structure of the... 

Fig. 1 The human IAP protein family. Human IAP proteins contain one or three baculovirus IAP repeat (BIR) domains. Several IAP family members also have RING (really interesting new gene) and UBA (ubiquitin associated) domains. The c-IAPl and C-IAP2 proteins each contain a caspase recruitment domain (CARD). Survivin contains a coiled coil domain NAIP has NACHT (domain present in NAIP, CIITA, HET-E, TP1) and leucine rich repeat (LRR) domains Apollon possesses a ubiquitin conjugating (UBC) domain...

Figure 18.3 The mammalian lAP family. The distinct domains are shown for each lAP. (BIR—baculovirus lAP repeat CARD-caspase activation recruitment domain RING—really interesting new gene zinc finger LRR—leucine rich repeat NOD-nucleotide-binding oligomerization domain).

P.M., TMSl, a novel proapoptotic caspase recruitment domain protein, is atarget of methylation-induced gene silencing in human breast cancers. Cancer Res., 60 (22), 6242,2000. 

FasL binding induces the oligomerization of Fas via their death domains (DD) and the recruitment to the clustered receptors of the DD-containing adaptor molecule FADD. FADD contains an additional caspase recruitment domain, called death effector domain (DED), that binds to the DED of procaspase-8. Its activation initiates a cascade of proteolytic cleavages, involving downstream... 

Apaf-1 possesses a region homologous to the procaspase-prodomain, known as the caspase-recruiting domain (CARD) at the N terminus, a region homologous to CED-4 in the middle part and WD-40 repeat structure that appears to be involved in protein-protein interactions. The released cytochrome c interacts with two cytosolic proteins, Apaf-1 and procaspase-9, and dATP/ATP in the cytoplasm to form a complex known as... 

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