Drosophila IKK-related kinase regulates nonapoptotic function of caspases, via degradation of IAPs
Drosophila IKK-related kinase regulates nonapoptotic function of caspases, via degradation of IAPs
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DOI：
10.1016/j.cell.2006.05.048
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发表时间：
2006-08-11
期刊：
影响因子：
64.5
通讯作者：
Miura, Masayuki
中科院分区：
文献类型：
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作者：
Kuranaga, Erina;Kanuka, Hirotaka;Miura, Masayuki
在细胞凋亡的背景下，半胱天冬酶激活已被广泛研究。然而，半胱天冬酶也控制其他细胞功能，尽管在非凋亡背景下调节半胱天冬酶的机制仍然不清楚。Drosophila IAP1（DIAP1）是一种内源性半胱天冬酶抑制剂，在发育过程中调节细胞死亡至关重要。在这里，我们描述了果蝇IKK相关激酶（DmIKK）作为一种调节剂的半胱天冬酶激活在非凋亡的情况下。我们发现DmIKK β通过直接磷酸化促进DIAP 1的降解。敲低DmIKK β在前神经簇的翅膀成虫盘，其中非凋亡的半胱天冬酶活性是必要的适当的感觉器官前体（SOP）的发展，稳定内源性DIAP 1和影响果蝇SOP的发展。我们的研究结果表明，DmIKK β是DIAP 1蛋白水平的决定因素，它建立了执行非凋亡caspase功能所需的活性阈值。
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 (DmIKK epsilon) as a regulator of caspase activation in a nonapoptotic context. We show that DmIKK epsilon promotes degradation of DIAP1 through direct phosphorylation. Knockdown of DmIKK epsilon 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 DmIKK epsilon is a determinant of DIAP1 protein levels and that it establishes the threshold of activity required for the execution of nonapoptotic caspase functions.