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首页> 外文期刊>Cell death and differentiation >The deubiquitinating enzyme DUBAI stabilizes DIAP1 to suppress Drosophila apoptosis
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The deubiquitinating enzyme DUBAI stabilizes DIAP1 to suppress Drosophila apoptosis

机译：去泛素化酶DUBAI稳定DIAP1以抑制果蝇凋亡

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摘要

Deubiquitinating enzymes (DUBs) counteract ubiquitin ligases to modulate the ubiquitination and stability of target signaling molecules. In Drosophila, the ubiquitin-proteasome system has a key role in the regulation of apoptosis, most notably, by controlling the abundance of the central apoptotic regulator DIAP1. Although the mechanism underlying DIAP1 ubiquitination has been extensively studied, the precise role of OUB(s) in controlling DIAP1 activity has not been fully investigated. Here we report the identification of a DIAP1 -directed OUB using two complementary approaches. First, a panel of putative Drosophila DUBs was expressed in S2 cells to determine whether DIAP1 could be stabilized, despite treatment with death-inducing stimuli that would induce DIAP1 degradation. In addition, RNAi fly lines were used to detect modifiers of DIAP1 antagonist-induced cell death in the developing eye. Together, these approaches identified a previously uncharacterized protein encoded by CG8830, which we named DeUBiquitinating-Apoptotic-lnhibitor (DUBAI), as a novel DUB capable of preserving DIAP1 to dampen Drosophila apoptosis. DUBAI interacts with DIAP1 in S2 cells, and the putative active site of its DUB domain (C367) is required to rescue DIAP1 levels following apoptotic stimuli. DUBAI, therefore, represents a novel locus of apoptotic regulation in Drosophila, antagonizing cell death signals that would otherwise result in DIAP1 degradation.
机译：去泛素化酶（DUB）抵消了泛素连接酶，以调节靶信号分子的泛素化和稳定性。在果蝇中，泛素-蛋白酶体系统在调节细胞凋亡中起关键作用，最显着的是通过控制中央凋亡调节因子DIAP1的丰度。尽管深入研究了DIAP1泛素化的机制，但尚未充分研究OUB在控制DIAP1活性中的确切作用。在这里，我们报告了使用两种互补方法对DIAP1定向OUB的鉴定。首先，尽管使用了会诱导DIAP1降解的诱导死亡的刺激物进行治疗，但仍在S2细胞中表达了一组假定的果蝇DUB，以确定DIAP1是否可以稳定。此外，RNAi飞线用于检测DIAP1拮抗剂诱导的发育中细胞死亡的修饰因子。总之，这些方法确定了由CG8830编码的先前未表征的蛋白质，我们将其命名为DeUBiquitinating-Apoptotic-Inhibitor（DUBAI），作为一种能够保留DIAP1来抑制果蝇凋亡的新型DUB。 DUBAI与S2细胞中的DIAP1相互作用，并需要其DUB结构域的假定活性位点（C367）来在凋亡刺激后恢复DIAP1水平。因此，DUBAI代表果蝇中新的凋亡调控基因座，拮抗细胞死亡信号，否则将导致DIAP1降解。

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