Apoptosis is the process of programmed cell death executed by specific proteases, the caspases, which mediate the cleavage of various vital proteins. Elucidating the consequences of this endoproteolytic cleavage is crucial to understanding cell death and other related biological processes. Although a number of possible roles for caspase-6 have been proposed, the identities and functions of prot...

Excitotoxicity, oxidative stress, and apoptosis have been recognized as routes to neuronal death in various neurological diseases. We examined the possibility that PHF-1 tau, a substrate for various proteases, would be selectively cleaved depending upon routes of neuronal death. Cleavage form of PHF-1 tau was not observed in cortical cell cultures exposed to excitotoxins or oxidative stress tha...

Tight control of apoptosis is required for proper development and maintenance of homeostasis in multicellular organisms. Cells can protect themselves from potentially lethal stimuli by expressing antiapoptotic factors, such as inhibitors of apoptosis, FLICE (caspase 8)-inhibitory proteins, and members of the Bcl2 family. Here, we describe a mechanism that allows cells to survive once executione...

A transient, sublethal ischemic interval confers resistance to a subsequent, otherwise lethal ischemic insult, in a process termed ischemic preconditioning. Poly(ADP-ribose) polymerase-1 (PARP-1) normally functions in DNA repair, but extensive PARP-1 activation is a major cause of ischemic cell death. Because PARP-1 can be cleaved and inactivated by caspases, we investigated the possibility tha...

During apoptosis, the activation of a family of cysteine proteases, or caspases, results in proteolytic cleavage of numerous substrates. Antibody probes specific for neoepitopes on protein fragments generated by caspase cleavage provide a means to monitor caspase activity at the level of the individual cell. Poly (ADP-ribose) polymerase (PARP), a nuclear enzyme involved in DNA repair, is a well...

Ets-1 is a transcription factor that plays an important role in various physiological and pathological processes, such as development, angiogenesis, apoptosis and tumour invasion. In the present study, we have demonstrated that Ets-1 p51, but not the spliced variant Ets-1 p42, is processed in a caspase-dependent manner in Jurkat T-leukaemia cells undergoing apoptosis, resulting in three C-termi...

The extracellular ligand-induced extrinsic pathway of apoptosis is executed via caspase protease cascades that activate downstream effectors by means of site-directed proteolysis. Here we identify proteome changes upon the induction of apoptosis by the cytokine tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in a Jurkat T cell line. We detected caspase-dependent cleavage substra...

Dietary phytochemicals have been shown to be protective against various types of cancers. However, the precise underlying protective mechanisms are poorly understood. In the present study, we report that treatment of A549 cells with quercetin resulted in a dose-dependent reduction in cell viability and DNA synthesis with the rate of apoptosis equivalent to 1.2 +/- 0.8, 6.3 +/- 0.9, 16.5 +/- 1.5...

In mammalian cells, the Golgi apparatus undergoes extensive fragmentation during apoptosis. p115 is a key vesicle tethering protein required for maintaining the structural organization of the Golgi apparatus. Here, we demonstrate that p115 was cleaved during apoptosis by caspases 3 and 8. Compared with control cells expressing native p115, those expressing a cleavage-resistant form of p115 dela...

A subgroup of caspase family of inflammatory caspases (-1, -4, -5, -11, and -12) play important role during cytokine maturation and inflammation but their regulation is not well understood as much as the initiator and effector caspases. Here, the biochemical mechanism of caspase-4 activation is elucidated. With citrate, a well-known kosmotrope to enhance the monomer-dimer transition, caspase-4 ...