TY - JOUR
T1 - Drosophila IKK-Related Kinase Regulates Nonapoptotic Function of Caspases via Degradation of IAPs
AU - Kuranaga, Erina
AU - Kanuka, Hirotaka
AU - Tonoki, Ayako
AU - Takemoto, Kiwamu
AU - Tomioka, Takeyasu
AU - Kobayashi, Masatomo
AU - Hayashi, Shigeo
AU - Miura, Masayuki
N1 - Funding Information:
We thank M. Sato, S. Kondo, Y. Takei-Yamaguchi, T. Awasaki, K. Ito, T. Tabata, Y. Hiromi, R. Takahashi, B. Hay, S. Yanagawa, P. Simpson, M. Bourouis, H. Bellen, R. Ueda, H. Richardson, R. Phillips, R. Carthew, V. Rodrigues, H. Steller, T. Kozlova, J. Nambu, M. Nakanishi, A. Gould, and K. Kimura for fly strains and materials; the Developmental Studies Hybridoma Bank for antibodies; the Berkeley Drosophila Genome Project for providing various reagents and information; and the Drosophila Genetic Resource Center (Kyoto Institute of Technology) and the Bloomington Drosophila Stock Center for fly stocks. We are grateful to H. Okano for kind support and encouragement. We are also grateful to K. Oshima for discussions; B. Nelson for critical reading; H. Ichijo, T. Takeda, and H. Nishitoh for valuable suggestions; and the entire Miura lab for technical support and helpful discussion. This work was supported in part by grants from the Suzuken Memorial Foundation to E.K. and the Takeda Science Foundation to E.K. and M.M. This work was also supported in part by grants from the Japanese Ministry of Education, Science, Sports, Culture and Technology to E.K., H.K., and M.M. H.K. was supported by the Program for Promotion of Basic Research Activities for Innovative Biosciences (PROBRAIN). M.M. was supported in part by a RIKEN Bioarchitect Research Grant, the TORAY Science Foundation, the Cell Science Research Foundation, and the Astellas Foundation for Research on Metabolic Disorders.
PY - 2006/8/4
Y1 - 2006/8/4
N2 - Caspase activation has been extensively studied in the context of apoptosis. However, caspases also control other cellular functions, although the mechanisms regulating caspases in nonapoptotic contexts remain obscure. Drosophila IAP1 (DIAP1) is an endogenous caspase inhibitor that is crucial for regulating cell death during development. Here we describe Drosophila IKK-related kinase (DmIKKε) as a regulator of caspase activation in a nonapoptotic context. We show that DmIKKε promotes degradation of DIAP1 through direct phosphorylation. Knockdown of DmIKKε in the proneural clusters of the wing imaginal disc, in which nonapoptotic caspase activity is required for proper sensory organ precursor (SOP) development, stabilizes endogenous DIAP1 and affects Drosophila SOP development. Our results demonstrate that DmIKKε is a determinant of DIAP1 protein levels and that it establishes the threshold of activity required for the execution of nonapoptotic caspase functions.
AB - Caspase activation has been extensively studied in the context of apoptosis. However, caspases also control other cellular functions, although the mechanisms regulating caspases in nonapoptotic contexts remain obscure. Drosophila IAP1 (DIAP1) is an endogenous caspase inhibitor that is crucial for regulating cell death during development. Here we describe Drosophila IKK-related kinase (DmIKKε) as a regulator of caspase activation in a nonapoptotic context. We show that DmIKKε promotes degradation of DIAP1 through direct phosphorylation. Knockdown of DmIKKε in the proneural clusters of the wing imaginal disc, in which nonapoptotic caspase activity is required for proper sensory organ precursor (SOP) development, stabilizes endogenous DIAP1 and affects Drosophila SOP development. Our results demonstrate that DmIKKε is a determinant of DIAP1 protein levels and that it establishes the threshold of activity required for the execution of nonapoptotic caspase functions.
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U2 - 10.1016/j.cell.2006.05.048
DO - 10.1016/j.cell.2006.05.048
M3 - Article
C2 - 16887178
AN - SCOPUS:33746570157
VL - 126
SP - 583
EP - 596
JO - Cell
JF - Cell
SN - 0092-8674
IS - 3
ER -