Drosophila IKK-Related Kinase Regulates Nonapoptotic Function of Caspases via Degradation of IAPs

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 re...

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Bibliographic Details
Published in:Cell 2006-08, Vol.126 (3), p.583-596
Main Authors: Kuranaga, Erina, Kanuka, Hirotaka, Tonoki, Ayako, Takemoto, Kiwamu, Tomioka, Takeyasu, Kobayashi, Masatomo, Hayashi, Shigeo, Miura, Masayuki
Format: Article
Language:English
Subjects:
Animals
Apoptosis - genetics
Caspases - genetics
Caspases - metabolism
Cells, Cultured
Down-Regulation - genetics
Drosophila
Drosophila melanogaster - cytology
Drosophila melanogaster - embryology
Drosophila melanogaster - metabolism
Drosophila Proteins - genetics
Drosophila Proteins - metabolism
Embryo, Nonmammalian - cytology
Embryo, Nonmammalian - embryology
Embryo, Nonmammalian - metabolism
Embryonic Development - genetics
Gene Expression Regulation, Developmental - genetics
I-kappa B Kinase - genetics
I-kappa B Kinase - metabolism
Inhibitor of Apoptosis Proteins - genetics
Inhibitor of Apoptosis Proteins - metabolism
Phosphorylation
Sense Organs - abnormalities
Sense Organs - cytology
Sense Organs - metabolism
Wings, Animal - abnormalities
Wings, Animal - cytology
Wings, Animal - metabolism
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Summary: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 (DmIKKɛ) as a regulator of caspase activation in a nonapoptotic context. We show that DmIKKɛ promotes degradation of DIAP1 through direct phosphorylation. Knockdown of DmIKKɛ 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 DmIKKɛ is a determinant of DIAP1 protein levels and that it establishes the threshold of activity required for the execution of nonapoptotic caspase functions.
ISSN:0092-8674
1097-4172
DOI:10.1016/j.cell.2006.05.048