Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.61 (caspase-8)
 6,833 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

IFNs are a family of cytokines with pleiotropic biological effects mediated by scores of responsive genes. IFNs were the first human proteins to be effective in cancer therapy and were among the first recombinant DNA products to be used clinically. Both quality and quantity of life has been improved in response to IFNs in various malignancies. Despite its beneficial effects, unraveling the mechanisms of the anti-tumor effects of IFN has proven to be a complex task. IFNs may mediate anti-tumor effects either indirectly by modulating immunomodulatory and anti-angiogenic responses or by directly affecting proliferation or cellular differentiation of tumor cells. Both direct or indirect effects of IFNs result from induction of a subset of genes, called IFN stimulated genes (ISGs). In addition to the ISGs implicated in anti-viral, anti-angiogenic, immunomodulatory and cell cycle inhibitory effects, oligonucleotide microarray studies have identified ISGs with apoptotic functions. These include TNF-alpha related apoptosis inducing ligand (TRAIL/Apo2L), Fas/FasL, XIAP associated factor-1 (XAF-1), caspase-4, caspase-8, dsRNA activated protein kinase (PKR), 2'5'A oligoadenylate synthetase (OAS), death activating protein kinases (DAP kinase), phospholipid scramblase, galectin 9, IFN regulatory factors (IRFs), promyelocytic leukemia gene (PML) and regulators of IFN induced death (RIDs). In vitro IFN-alpha, IFN-beta and IFN-gamma induced apoptosis in multiple cell lines of varied histologies. This review will emphasize possible mechanisms and the role of ISGs involved in mediating apoptotic function of IFNs.
 ...
PMID:Apoptosis and interferons: role of interferon-stimulated genes as mediators of apoptosis. 1276 84

Coordinated regulation of autophagy and apoptosis helps to enhance the antitumor effects of sodium selenite. However, the potential molecules that act as switch nodes in the crosstalk between autophagy and apoptosis is still elusive. Phospholipid scramblase 1 (PLSCR1) has been shown to regulate leukocyte differentiation, while its role in autophagy/apoptosis toggle switch remains unexplored. In this study, we showed that sodium selenite switched protective autophagy to apoptosis in p53-wild type NB4 cells without obvious caspase-8/apoptosis-inducing factor (AIF) axis activation, while induced autophagy-dependent caspase-8/AIF axis activation in p53-mutant Jurkat cells. Additionally, p53 was demonstrated as a positive regulator of PLSCR1. p53-dependent up-regulation of PLSCR1 accounted for the differential regulation of autophagy and apoptosis induced by sodium selenite. Furthermore, sodium selenite induced the release of AIF from mitochondria to cytosol with the facilitation of caspase-8 in Jurkat cells, while not in NB4 cells. The released AIF further enhanced autophagy flux through interacting with PLSCR1, which hereby resulting in the disassociation of PLSCR1 from Atg5-Atg12 complex. Our results indicate that PLSCR1 plays a critical role in p53-dependent regulation of autophagy and apoptosis in sodium selenite-treated leukemia cells. Manipulation of p53-PLSCR1 cascade might be beneficial to enhance the anti-tumor effects of sodium selenite.
 ...
PMID:p53 controls the switch between autophagy and apoptosis through regulation of PLSCR1 in sodium selenite-treated leukemia cells. 3201 28