We evaluated the effect of the human immunodeficiency virus (HIV) protease inhibitor saquinavir on the imatinib-sensitive and imatinib-resistant chronic myelogenous leukemia cell lines. Saquinavir, which is also a proteasome blocker, showed dose- and time-related anti-proliferative activity, particularly on the imatinib-resistant lines and a pro-apoptotic effect. Association with imatinib cause...

Two novel synthetic tetrapeptides, VEID-CHO and DMQD-CHO, could selectively inhibit caspase-6 and caspase-3, respectively. We used these inhibitors to dissect the pathway of caspase activation in Fas-stimulated Jurkat cells and identify the roles of each active caspase in apoptotic processes. Affinity labeling techniques revealed a branched protease cascade in which caspase-8 activates caspase-...

DNA-dependent protein kinase (DNA-PK) consists of a 460 kDa subunit that contains the catalytic domain (DNA-PKcs) complexed with two polypeptides of 70 kDa and 80 kDa (Ku70 and Ku80) which comprise the Ku autoantigen. DNA-PKcs requires association with DNA via Ku for catalytic activation and is implicated in double strand break repair, V(D)J recombination and transcription. We have utilised a c...

The intriguing cell biology of apoptotic cell death results in the externalization of numerous autoantigens on the apoptotic cell surface, including protein determinants for specific recognition, linked to immune responses. Apoptotic cells are recognized by phagocytes and trigger an active immunosuppressive response ("innate apoptotic immunity" (IAI)) even in the absence of engulfment. IAI is r...

PURPOSE In order to investigate the role of Fas on the chemosensitivity of cancer cells in regards to chemotherapeutic agents, the Fas/FasL signaling pathway of apoptosis was explored in human hepatoma cells. MATERIALS AND METHODS Fas expression of hepatoma cells including Chang, Huh7, HepG2, and Hep3B cells, was determined by RT-PCR and flow cytometry analysis. Cell viability was measured by...

OBJECTIVE Vascular smooth muscle cell (VSMC) apoptosis occurs at low levels in atherosclerotic plaques and in vessel remodeling; however, the consequences and mediators of these levels are not known. Akt1 protects against VSMC apoptosis largely through inactivating target proteins such as forkhead class O transcription factor 3a (FoxO3a), but Akt1 signaling is reduced and FoxO3a activity is inc...

We have characterized viral-cell interactions of hepatitis C virus (HCV) and liver cells to study the pathogenesis of HCV infection. HepG2 cells constitutively expressing HCV core protein showed apoptotic changes in response to stimulation with anti-Fas monoclonal antibody. Cells treated with the antibody showed extensive cell rounding, shrinkage, and cytoplasmic blebbing and finally detached f...

The yeast S. cerevisiae can undergo programmed cell death that exhibits the typical cellular markers of apoptosis. The mammalian HtrA2 protein was recently reported to mediate apoptosis in a serine-protease-dependent manner owing to its ability to antagonise the inhibitor of apoptosis protein XIAP. Here, we report the identification and characterisation of the S. cerevisiae HtrA-like protein, w...

Cytotoxic T lymphocytes (CTL) can induce apoptosis through a granzyme B-based killing mechanism. Here we show that in cells undergoing apoptosis by granzyme B, both p45 pro-interleukin 1 beta converting enzyme (ICE) and pro-CPP32 are processed. Using ICE deficient (ICE -/-) mice, embryonic fibroblasts exhibit high levels of resistance to apoptosis by granzyme B or granzyme 3, while B lymphoblas...

During programmed cell death, the clearance of apoptotic cells is achieved by their phagocytosis and delivery to lysosomes for destruction in engulfing cells. However, the role of lysosomal proteases in cell corpse destruction is not understood. Here we report the identification of the lysosomal cathepsin CPL-1 as an indispensable protease for apoptotic cell removal in Caenorhabditis elegans. W...