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By differential screening of tumor necrosis factor alpha (TNF-alpha) and lipopolysaccharide (LPS)- activated endothelial cells (ECs), we have identified a cDNA clone that turned out to be a member of the inhibitor of apoptosis (iap) gene family. iap genes function to protect cells from undergoing apoptotic death in response to a variety of stimuli. These(More)
Activation of caspase 1 is essential for the maturation and release of IL-1beta and IL-18 and occurs in multiprotein complexes, referred to as inflammasomes. The apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is the essential adaptor protein for recruiting pro-caspase 1 into inflammasomes, and consistently gene(More)
Bcl-2 is a key apoptosis regulatory protein of the mitochondrial death pathway whose function is dependent on its expression levels. Although Bcl-2 expression is controlled by various mechanisms, post-translational modifications, such as ubiquitination and proteasomal degradation, have emerged as important regulators of Bcl-2 function. However, the(More)
Cytosolic pathogen- and damage-associated molecular patterns are sensed by pattern recognition receptors, including members of the nucleotide-binding domain and leucine-rich repeat-containing gene family (NLR), which cause inflammasome assembly and caspase-1 activation to promote maturation and release of the inflammatory cytokines interleukin-1β (IL-1β)(More)
Proteins containing PAAD [pyrin, AIM (absent-in-melanoma), ASC [apoptosis-associated speck-like protein containing a CARD (caspase-recruitment domain)] and DD (death domain)-like] (PYRIN, DAPIN) domains are involved in innate immunity, regulating pathways leading to nuclear-factor-kappa B (NF-kappa B) and pro-caspase-1 activation. Many PAAD-family proteins(More)
The production of bio-active interleukin-1beta (IL-1beta), a pro-inflammatory cytokine, is mediated by activated caspase-1. One of the known molecular mechanisms underlying pro-caspase-1 processing and activation involves binding of the caspase-1 prodomain to a caspase recruitment domain (CARD)-containing serine/threonine kinase known as RIP2/CARDIAK/RICK.(More)
Pyrin domain (PYD) proteins have recently emerged as important signaling molecules involved in the development of innate immunity against intracellular pathogens through activation of inflammatory mediator pathways. ASC is the central adaptor protein, which links pathogen recognition by PYD-containing pathogen recognition receptors, known as PYD-Nod-like(More)
PYRIN domain (PYD) proteins have recently emerged as important signaling molecules involved in the development of innate immunity to intracellular pathogens through activation of inflammatory mediator pathways. ASC is the central adaptor protein, which links pathogen recognition by PYD-containing pathogen recognition receptors to the activation of(More)
Massive apoptosis of keratinocytes has been implicated in the pathogenesis of chemotherapy-induced skin toxicities, but the underlying mechanisms of action are not well understood. The present study investigated the apoptotic effect of doxorubicin (DOX) on HaCaT keratinocytes and determined the underlying mechanisms. Treatment of the cells with DOX induced(More)
Periodic fever syndromes (PFSs) comprise a subset of the hereditary autoinflammatory disorders that are defined by recurrent self-resolving attacks of systemic inflammatory reactions in the absence of infection or autoimmunity. Recent advances have led to the discovery that members of a new family of genes, the PYRIN family, account for several hereditary(More)