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Citation
Wu, Y., Lindblad, J.L., Garnett, J., Kamber Kaya, H.E., Xu, D., Zhao, Y., Flores, E.R., Hardy, J., Bergmann, A. (2016). Genetic characterization of two gain-of-function alleles of the effector caspase DrICE in Drosophila.  Cell Death Differ. 23(4): 723--732.
FlyBase ID
FBrf0231218
Publication Type
Research paper
Abstract

Caspases are the executioners of apoptosis. Although much is known about their physiological roles and structures, detailed analyses of missense mutations of caspases are lacking. As mutations within caspases are identified in various human diseases, the study of caspase mutants will help to elucidate how caspases interact with other components of the apoptosis pathway and how they may contribute to disease. DrICE is the major effector caspase in Drosophila required for developmental and stress-induced cell death. Here, we report the isolation and characterization of six de novo drICE mutants, all of which carry point mutations affecting amino acids conserved among caspases in various species. These six mutants behave as recessive loss-of-function mutants in a homozygous condition. Surprisingly, however, two of the newly isolated drICE alleles are gain-of-function mutants in a heterozygous condition, although they are loss-of-function mutants homozygously. Interestingly, they only behave as gain-of-function mutants in the presence of an apoptotic signal. These two alleles carry missense mutations affecting conserved amino acids in close proximity to the catalytic cysteine residue. This is the first time that viable gain-of-function alleles of caspases are described in any intact organism and provides a significant exception to the expectation that mutations of conserved amino acids always abolish the pro-apoptotic activity of caspases. We discuss models about how these mutations cause the gain-of-function character of these alleles.

PubMed ID
PubMed Central ID
PMC4986642 (PMC) (EuropePMC)
Related Publication(s)
Personal communication to FlyBase

Location data for Drice alleles.
Wu and Bergmann, 2016.9.7, Location data for Drice alleles. [FBrf0233385]

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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Cell Death Differ.
    Title
    Cell Death and Differentiation
    Publication Year
    1994-
    ISBN/ISSN
    1350-9047
    Data From Reference
    Alleles (10)
    Genes (3)
    Transgenic Constructs (2)