Caspase family

Apoptotic executioner caspases (caspase-3, -6, -7) constitute a subgroup of the caspase family. These proteases are the workhorses of the apoptotic process as they are responsible for cleaving many down-stream substrates important for cellular morphology, organelle homeostasis, cell cycle arrest, and regulation of transcription and translation. 

Apoptotic initiator caspases (caspase-2, -8, -9 and -10) constitute a subgroup of the caspase family. These caspases are the first to become proteolytically active in the apoptotic cascade. Their activation takes place in multiprotein complexes initiated by pro-apoptotic stimuli, such as TNFa, a-Fas, staurosporine. Once activated, they can process their substrates, which include the apoptotic executioner caspases. 

Apoptosis occurs as a result of a cascade ofproteolysis that culminates in the destruction of the cell. Apoptotic proteolysis is catalyzed by the caspase family of... 

Inflammatory caspases (caspase-1, -4, -5,-11 and -12) constitute a subgroup of the caspase family. Caspase-1 is the best characterized member and is responsible for the proteolytic maturation and release of the pro-inflammatory cytokines pro-interleukin (IL)-1 (3 and pro-IL-18. Caspase-1 gets activated in inflammasome complexes upon cellular stress, cellular damage and infection. 

Regulation of programmed cell death (apoptosis) is not only important in normal cell development and homeostasis [1, 2], but also during the process of carcinogenesis [3], Apoptosis is suppressed in most cancer cells and induction of apoptosis is one cancer treatment strategy [4], There are many processes and factors that can be modulated to induce cancer cell apoptosis, such as regulation of factors involved in cell cycle arrest [5], protein kinase modulation [6], caspase family activation [7], and the balance in expression between Bcl-2 family members [8],... 

Endres, M., Namura, S., Shimizu-Sasamata, M., Waeber, C., Zhang, L., Gomez-Isla, T., Hyman, B.T., and Moskowitz, M.A., Attenuation of delayed neuronal death after mild focal ischemia in mice by inhibition of the caspase family, /. Cereb. Blood Flow Metab., 18, 238,1998. 

J., Chapman, K., Nicholson, D. A combinatorial approach defines specificities of members of the caspase family and Granzyme B. 

We will synthesize a 6,000-member focused library designed to inhibit the caspase family of cysteine proteases involved in apoptosis. 

Both mature and nascent forms of ErbB-2 are sensitive to geldanamycin. The drug seems to prevent exit of nascent ErbB-2 from the endoplasmic reticulum (Chavany et al. 1996), and directs the precursor to degradation by the proteasome (Mimnaugh et al. 1996). Sensitivity of ErbB-2 is conferred by the kinase domain of the receptor, but the functionality of the kinase is not necessary, as a kinase-defective mutant of ErbB-2 is also sensitive to geldanamycin (Xu et al. 2001). ErbB-2 is subject to a complex form of degradation, involving the sequential activity of a caspase family protease that cleaves the carboxyl-terminal tail of the receptor from the rest of the molecule (Tikhomirov and Carpenter 2000 Tikhomirov and Carpenter 2001). The cytoplasmic part is ubiquitinated and is subjected to... 

R, Schotte, R, Van Criekinge, W., Beyaert, R., and Piers, W., Characterization of seven murine caspase family members. FEES Lett. 403, 61-69 (1997). 

W13. Wolf, B. B., and Green, D. R., Suicidal tendencies Apoptotic cell death by caspase family proteinases. J. Biol. Chem. 274, 20049-20052 (1999). 

The nucleotide sequence of the ced-3 gene revealed that the Ced3 protein is closely related to the interleukin-converting enzyme ICE,149-152 which is discussed on p. 619. ICE is a member of the caspase family of thiol proteases (p. 619). At least 14 different caspases are found in the human body. Some of them... 

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). 

The most common strategies consist of developing recombinant cell lines expressing antiapoptotic genes that regulate the two main families of proteins involved in the apoptotic cascade the Bcl-2 and caspase families. 

Thornberry NA, Rano TA, Peterson EP, Rasper DM, Timkey T, Garcia-Calvo M, Houtzager VM, Nordstrom PA, Roy S, Vaillancourt JP, Chapman KT, Nicholson DW (1997), A combinatorial approach defines specificities of members of the caspase family and granzyme B. Functional relationships established for key... 

The apoptotic process is mediated by the caspase family of cysteine protease. Caspases are implicated both in the induction and execution of the death sentence. Apoptosis can be induced by (1) activation of death receptors, such as Fas, which recruits procaspase 8 via adaptor proteins and promotes its autocatalytic activation, and (2) the release of cytochrome C from mitochondria by DNA damaging drugs and other chemotherapeutic agents (Figure 7.11). 

N. A. Thornberry, T. A. Rano, E. P. Peterson, D. M. Rasper, T. Timkey, M. Garda Calvti, et al. B combinatorial approach defines specifidties of members of the caspase family and granzyme B. Functional relationships established for key mediators of apoptosis. Jf Biol Chem, 272 (29), 17907-17911, 1997. 

The family of cysteine proteases, which are called caspases, plays a major role in the execution of apoptotic cell death (12). Many studies suggest that increased apoptosis and caspase activity contribute to tissue damage in both acute (e.g., myocardial infarction, stroke, sepsis, spinal cord injury) and chronic (e.g., Alzheimer s, Parkinson s, Huntington s disease) human diseases (13,14). Caspase family members are also prominently... 

Most caspase-inhibitor design strategies target their active sites and are based on caspase substrate preferences. Tetrapep-tide inhibitors, which are based on identihed sequences of the four amino acid recognition motifs, were shown to inhibit caspase family members selectively (24) (Fig. 2a). Overall, a typical peptide-based caspase inhibitor consists of three major structural components ... 

Wolf B, Green D. Suicidal tendencies apoptotic cell death by caspase family proteinases. J Biol Chem 1999 274 20049-20052. Ahmad M, Srinivasula SM, Hegde R, Mukattash R, Eernandes-AlnemriT, Alnemri ES. Identification and characterization of murine caspase 14, a new member of the caspase family. Cancer Res 1998 58 5201-5205. 

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