期刊
CELL DEATH AND DIFFERENTIATION
卷 14, 期 1, 页码 92-102出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.cdd.4401931
关键词
ARK; Drosophila; WD40; apoptosis; Apaf-1
资金
- NATIONAL CANCER INSTITUTE [P30CA016672] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM068016] Funding Source: NIH RePORTER
- NCI NIH HHS [P30 CA016672, CA16672] Funding Source: Medline
- NIGMS NIH HHS [R01 GM068016-04, R01 GM068016, GM068016] Funding Source: Medline
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.
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