TY - JOUR
T1 - Caspy, a zebrafish caspase, activated by ASC oligomerization is required for pharyngeal arch development
AU - Masumoto, Junya
AU - Zhou, Weibin
AU - Chen, Felicia F.
AU - Su, Fengyun
AU - Kuwada, John Y.
AU - Hidaka, Eiko
AU - Katsuyama, Tsutomu
AU - Sagara, Junji
AU - Taniguchi, Shun'ichiro
AU - Ngo-Hazelett, Phuong
AU - Postlethwait, John H.
AU - Núñez, Gabriel
AU - Inohara, Naohiro
PY - 2003/2/7
Y1 - 2003/2/7
N2 - The pyrin domain was identified recently in multiple proteins that are associated with apoptosis and/or inflammation, but the physiological and molecular function of these proteins remain poorly understood. We have identified Caspy and Caspy2, two zebrafish caspases containing N-terminal pyrin domains. Expression of Caspy and Caspy2 induced apoptosis in mammalian cells that were inhibited by general caspase inhibitors. Biochemical analysis revealed that both Caspy and Caspy2 are active caspases, but they exhibit different substrate specificity. Caspy, but not Caspy2, interacted with the zebrafish orthologue of ASC (zAsc), a pyrin- and caspase recruitment domain-containing protein identified previously in mammals. The pyrin domains of both Caspy and zAsc were required for their interaction. Furthermore, zAsc and Caspy co-localized to the "speck" when co-transfected into mammalian cells. Enforced oligomerization of zAsc, but not simple interaction with zAsc, induced specific proteolytic activation of Caspy and enhanced Caspy-dependent apoptosis. Injection of zebrafish embryos with a morpholino antisense oligonucleotide corresponding to caspy resulted in an "open mouth" phenotype associated with defective formation of the cartilaginous pharyngeal skeleton. These studies suggest that zAsc mediates the activation of Caspy, a caspase that plays an important role in the morphogenesis of the jaw and gill-bearing arches.
AB - The pyrin domain was identified recently in multiple proteins that are associated with apoptosis and/or inflammation, but the physiological and molecular function of these proteins remain poorly understood. We have identified Caspy and Caspy2, two zebrafish caspases containing N-terminal pyrin domains. Expression of Caspy and Caspy2 induced apoptosis in mammalian cells that were inhibited by general caspase inhibitors. Biochemical analysis revealed that both Caspy and Caspy2 are active caspases, but they exhibit different substrate specificity. Caspy, but not Caspy2, interacted with the zebrafish orthologue of ASC (zAsc), a pyrin- and caspase recruitment domain-containing protein identified previously in mammals. The pyrin domains of both Caspy and zAsc were required for their interaction. Furthermore, zAsc and Caspy co-localized to the "speck" when co-transfected into mammalian cells. Enforced oligomerization of zAsc, but not simple interaction with zAsc, induced specific proteolytic activation of Caspy and enhanced Caspy-dependent apoptosis. Injection of zebrafish embryos with a morpholino antisense oligonucleotide corresponding to caspy resulted in an "open mouth" phenotype associated with defective formation of the cartilaginous pharyngeal skeleton. These studies suggest that zAsc mediates the activation of Caspy, a caspase that plays an important role in the morphogenesis of the jaw and gill-bearing arches.
UR - http://www.scopus.com/inward/record.url?scp=0037423284&partnerID=8YFLogxK
U2 - 10.1074/jbc.M203944200
DO - 10.1074/jbc.M203944200
M3 - Article
C2 - 12464617
AN - SCOPUS:0037423284
SN - 0021-9258
VL - 278
SP - 4268
EP - 4276
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 6
ER -