ARK, the Apaf-1 related killer in Drosophila, requires diverse domains for its apoptotic activity
ARK, the Apaf-1 related killer in Drosophila, requires diverse domains for its apoptotic activity
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DOI：
10.1038/sj.cdd.4401931
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发表时间：
2007-01-01
影响因子：
12.4
通讯作者：
Bergmann, A.
中科院分区：
文献类型：
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作者：
Srivastava, M.;Scherr, H.;Bergmann, A.
在哺乳动物和果蝇中，凋亡半胱天冬酶分别受CED-4样蛋白Apaf-1和方舟的阳性控制。在EMS诱变筛选中，我们分离出33个方舟突变体作为隐性抑制hid诱导的细胞凋亡。方舟突变体是功能丧失的等位基因，其特征是发育性细胞凋亡减少。使用这些等位基因的表型系列，我们确定螺旋结构域I的核苷酸寡聚化结构域的关键方舟的凋亡活性。有趣的是，WD 40区域也可能对方舟的凋亡活性具有意想不到的正向需求。考虑到结构信息，我们讨论了这些结构域的组装和活动的方舟染色体的作用，并提出，WD 40区域是抗凋亡的细胞凋亡信号的情况下，和促凋亡的存在下，这样的信号。此外，一个明确的无效等位基因揭示了大多数，但不是所有的细胞凋亡所需的方舟，这表明存在一个不依赖于方舟的细胞凋亡途径。
In mammals and Drosophila, apoptotic caspases are under positive control of the CED-4-like proteins Apaf-1 and ARK, respectively. In an EMS-mutagenesis screen, we isolated 33 ark mutants as recessive suppressors of hid-induced apoptosis. The ark mutants are loss-of-function alleles characterized by reduced developmental apoptosis. Using the phenotypic series of these alleles, we identified helical domain I in the nucleotide oligomerization domain as critical for ARK's apoptotic activity. Interestingly, the WD40 region may also have an unanticipated positive requirement for the apoptotic activity of ARK. Considering structural information, we discuss the roles of these domains for assembly and activity of the ARK apoptosome, and propose that the WD40 region is anti-apoptotic in the absence of apoptotic signals, and pro-apoptotic in the presence of such signals. Furthermore, a defined null allele reveals that ark is required for most, but not all apoptosis suggesting the existence of an ARK-independent apoptotic pathway.