Members of the caspase family of cysteine proteases coordinate cell death through restricted proteolysis of diverse protein substrates and play a conserved role in apoptosis from nematodes to man. However, while numerous substrates for the mammalian cell death-associated caspases have now been described, few caspase substrates have been identified in other organisms. Here, we have utilized a pr...

If one were to take a moral view of cell activities, the caspases would be condemned on two counts. They not only give the order to kill cells, they also carry it out. But in the real-life utilitarian world of the cell, all this killing is simply a means to an end. Programmed cell death, or apoptosis, plays an important role in embryonic development and in protecting the body from damaged or ag...

During development, programmed cell death is regulated by cell-cell signals that either promote or inhibit caspase activation (Meier et al., 2000a). The biochemical mechanisms of extracellular regulation are incompletely known. Here, they have been studied using an antibody to detect caspase activation in vivo. Caspases are a class of intracellular cysteine proteases that cause cell death by cl...

We have compared cytoplasmic extracts from chicken DU249 cells at various stages along the apoptotic pathway. Extracts from morphologically normal "committed stage" cells induce apoptotic morphology and DNA cleavage in substrate nuclei but require ongoing caspase activity to do so. In contrast, extracts from frankly apoptotic cells induce apoptotic events in added nuclei in a caspase-independen...

Most developmentally programmed cell death in metazoans is mediated by caspases. During Drosophila metamorphosis, obsolete tissues, including the midgut and salivary glands, are removed by programmed cell death [1]. The initiator caspase Dronc and its activator Ark are required for the death of salivary glands, but not for midgut removal [2, 3]. In addition to caspases, complete removal of sali...

Apoptotic execution is characterized by dramatic changes in nuclear structure accompanied by cleavage of nuclear proteins by caspases (reviewed in [1]). Cell-free extracts have proved useful for the identification and functional characterization of activities involved in apoptotic execution [2-4] and for the identification of proteins cleaved by caspases [5]. More recent studies have suggested ...

The cytotoxic effect of anticancer drugs has been shown to involve induction of apoptosis. We report here that tumor cells resistant to CD95 (APO-1/Fas) -mediated apoptosis were cross-resistant to apoptosis-induced by anticancer drugs. Apoptosis induced in tumor cells by cytarabine, doxorubicin, and methotrexate required the activation of ICE/Ced-3 proteases (caspases), similarly to the CD95 sy...

Increasing evidence suggests that selective neuronal loss in neurodegenerative diseases involves activation of cysteine aspartyl proteases (caspases), which initiate and execute apoptosis. In Alzheimer disease both extracellular amyloid deposits and intracellular amyloid beta protein may activate caspases, leading to cleavage of nuclear and cytoskeletal proteins, including tau protein. Proteoly...

Specific Aims SA1. Determine which of the seven identified Drosophila caspase genes are expressed in Drosophila melanogaster S2 cells. SA2. Identify which of the expressed caspases are downstream of DIAP1 in the apoptosis pathway of S2 cells. SA3. Explore the order in which expressed initiator and effector caspases are activated and study the function of proteasomal degradation in regulating th...