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Targeted Delivery of an ADP-ribosylating Bacterial Toxin Into Cancer Cells
Abstract: The actin cytoskeleton, a central component of many cellular functions, is an attractive target for bacterial toxins. The ADP-ribosyltransferase TccC3 of the insect pathogen Photorhabdus luminescence modifies actin to force its aggregation. We intended to transport the catalytic part of this toxin preferentially into cancer cells. For this we used a toxin transporter which was redirected to the Epidermal Growth Factor Receptor (EGFR) or to the human EGF receptor 2 (HER2), which are overexpressed in several cancer cells. Protective antigen (PA) of anthrax toxin forms a pore through which the two catalytic parts of anthrax toxin (lethal factor and edema factor) or other proteins can ...
Alexander Lang
None
Inhibition of Arp2/3 Complex After ADP-ribosylation of Arp2 by Binary Clostridioides Toxins
Abstract: Clostridioides bacteria are responsible for life threatening infections. Here, we show that in addition to actin, the binary toxins CDT, C2I, and Iota from Clostridioides difficile, botulinum, and perfrigens, respectively, ADP-ribosylate the actin-related protein Arp2 of Arp2/3 complex and its additional components ArpC1, ArpC2, and ArpC4/5. The Arp2/3 complex is composed of seven subunits and stimulates the formation of branched actin filament networks. This activity is inhibited after ADP-ribosylation of Arp2. Translocation of the ADP-ribosyltransferase component of CDT toxin into human colon carcinoma Caco2 cells led to ADP-ribosylation of cellular Arp2 and actin followed by a collapse of the lamellipodial extensions and F-actin network. Exposure of isolated mouse colon pieces to CDT toxin induced the dissolution of the enterocytes leading to luminal aggregation of cellular debris and the collapse of the mucosal organization. Thus, we identify the Arp2/3 complex as hitherto unknown target of clostridial ADP-ribosyltransferases
The Big Book of Christmas Novels, Stories, Myths & Carols
The Big Book of Christmas Novels, Stories, Myths & Carols' is a monumental anthology that captivates the spirit of Christmas through a broad spectrum of literary forms, encompassing the timeless work of renowned authors from various periods and cultures. It is a collection that spans the gamut from the evocative and solemn to the joyous and lighthearted, effectively capturing the multifaceted essence of Christmas. The inclusion of works by literary giants such as William Shakespeare, Charles Dickens, and Leo Tolstoy, alongside tales by Hans Christian Andersen and the Brothers Grimm, showcases the anthologys rich diversity in storytelling and its profound grasp on themes of love, redemption, ...
The Most Wonderful Christmas Tales Of All Time
The Most Wonderful Christmas Tales Of All Time stands as an unparalleled anthology, uniting the works of classic authors whose writings have shaped the literary landscape of Christmas storytelling. This collection showcases an array of styles, from the poetic musings of William Wordsworth and Emily Dickinson to the compelling narratives of Leo Tolstoy and Fyodor Dostoevsky, offering readers a panoramic view of Christmas through various lenses of time, culture, and emotion. The anthology not only features tales of warmth and joy but also explores the depths of the human condition during this festive season, making it a profound study in the duality of the human experience. The ensemble of aut...
