RRC ID 5829
Author Kuranaga E, Kanuka H, Tonoki A, Takemoto K, Tomioka T, Kobayashi M, Hayashi S, Miura M.
Title Drosophila IKK-related kinase regulates nonapoptotic function of caspases via degradation of IAPs.
Journal Cell
Abstract 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 (DmIKKvarepsilon) as a regulator of caspase activation in a nonapoptotic context. We show that DmIKKvarepsilon promotes degradation of DIAP1 through direct phosphorylation. Knockdown of DmIKKvarepsilon 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 DmIKKvarepsilon is a determinant of DIAP1 protein levels and that it establishes the threshold of activity required for the execution of nonapoptotic caspase functions.
Volume 126(3)
Pages 583-96
Published 2006-8-11
DOI 10.1016/j.cell.2006.05.048
PII S0092-8674(06)00909-3
PMID 16887178
MeSH Animals Apoptosis / genetics Caspases / genetics Caspases / metabolism* Cells, Cultured Down-Regulation / genetics Drosophila Proteins / genetics Drosophila Proteins / metabolism* Drosophila melanogaster / cytology Drosophila melanogaster / embryology* Drosophila melanogaster / 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
IF 31.398
Times Cited 86