Caspases are the executioners of apoptosis. Although much is known about their physiological roles and structures, detailed analyses of missense mutations of @entity8782 are lacking. As mutations within @entity8782 are identified in various @entity1 diseases, the study of @entity20342 mutants will help to elucidate how @entity8782 interact with other components of the apoptosis pathway and how they may contribute to disease. DrICE is the major effector @entity20342 in @entity238 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 @entity3534 conserved among @entity8782 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 @entity3534 in close proximity to the catalytic @entity462 residue. This is the first time that viable gain-of-function alleles of @entity8782 are described in any intact organism and provides a significant exception to the expectation that mutations of conserved @entity3534 always abolish the pro-apoptotic activity of @entity8782 . We discuss models about how these mutations cause the gain-of-function character of these alleles.

Genetic characterization of two gain-of-function alleles of the effector XXXX DrICE in @entity238 .

@entity1 :: ('9606', 'Species') :: ['human'] @entity3534 :: ('MESH:D000596', 'Chemical') :: ['amino acids'] @entity462 :: ('MESH:D003545', 'Chemical') :: ['cysteine'] @entity8782 :: ('MESH:D056735', 'Disease') :: ['caspases'] @entity20342 :: ('37729(Tax:7227)', 'Gene') :: ['caspase'] @entity238 :: ('7227', 'Species') :: ['Drosophila']
@entity20342 :: (37729(Tax:7227),Gene) :: ['caspase']
