(Igaki et al., 2000) unveils the long anticipated, missing piece of the apoptosome in flies. On page 703 in this issue, in a paper by Colussi et al., Ku-mur, Richardson, and colleagues characterize the first Drosophila members of the Bcl-2 gene family whose function is important for programmed cell death (PCD). The founding member of this gene family was identified as the proto-oncogene upregul...

Cardiac remodeling is among the most important problems in patients with heart failure.1,2 Ventricular remodeling involves numerous processes, involving molecular alterations, myocardial changes, and the abnormal geometry of the chamber. As a consequence of myocardial infarction (MI), ventricular remodeling occurs immediately as an adaptive response to maintain cardiac output.3 However, ventric...

Granzyme B (GrB), acting similar to an apical caspase, efficiently activates a proteolytic cascade after intracellular delivery by perforin. Studies here were designed to learn whether the physiologic effector, GrB-serglycin, initiates apoptosis primarily through caspase-3 or through BH3-only proteins with subsequent mitochondrial permeabilization and apoptosis. Using four separate cell lines t...

Here, we identified caspase-2, protein kinase C (PKC)delta, and c-Jun NH2-terminal kinase (JNK) as key components of the doxorubicin-induced apoptotic cascade. Using cells stably transfected with an antisense construct for caspase-2 (AS2) as well as a chemical caspase-2 inhibitor, we demonstrate that caspase-2 is required in doxorubicin-induced apoptosis. We also identified PKCdelta as a novel ...

BACKGROUND Activation of caspases is crucial for the execution of apoptosis. Although the caspase cascade associated with activation of the initiator caspase-8 (CASP8) has been investigated in molecular and biochemical detail, the dynamics of CASP8 activation are not fully understood. METHODOLOGY/PRINCIPAL FINDINGS We have established a biosensor based on fluorescence resonance energy transfe...

Receptor-mediated apoptosis proceeds via two pathways: one requiring only a cascade of initiator and effector caspases (type I behavior) and the second requiring an initiator-effector caspase cascade and mitochondrial outer membrane permeabilization (type II behavior). Here, we investigate factors controlling type I versus II phenotypes by performing Lyapunov exponent analysis of an ODE-based m...

Apoptosis after the loss of cell anchorage--"anoikis"--plays an important role in the life cycle of adherent cells. Furthermore, loss of anchorage dependency is believed to be a critical step in metastatic transformation. The aim of this study was to further characterize the sequence of intracellular events during anoikis in a nontransformed population of human intestinal epithelial cells (IECs...

The enantioselective preparation of pharmacologically interesting chroman-fused spirooxindole derivatives is described based on an organocatalytic multicomponent cascade reaction. The compounds synthesized using this method potently inhibited the proliferation of various cancer cell lines. The most potent compound (7e) induced caspase-independent apoptosis and cell cycle arrest in MCF-7 breast ...

Premature ovarian failure (POF), an ovarian disorder of multifactorial origin, is defined as the occurrence of amenorrhea, hypergonadotropism and hypoestrogenism in females <40 years old. Apoptosis of ovarian granulosa cells is important in POF and understanding the regulatory mechanism underlying ovarian granulosa cell apoptosis may be beneficial for the management of POF. Increasing evidence ...