title: The biology of the cytolethal distending toxins.
abstract: The cytolethal distending toxins (CDTs), produced by a variety of Gram-negative pathogenic bacteria, are the first bacterial genotoxins described, since they cause DNA damage in the target cells. CDT is an A-B(2) toxin, where the CdtA and CdtC subunits are required to mediate the binding on the surface of the target cells, allowing internalization of the active CdtB subunit, which is functionally homologous to the mammalian deoxyribonuclease I. The nature of the surface receptor is still poorly characterized, however binding of CDT requires intact lipid rafts, and its internalization occurs via dynamin-dependent endocytosis. The toxin is retrograde transported through the Golgi complex and the endoplasmic reticulum, and subsequently translocated into the nuclear compartment, where it exerts the toxic activity. Cellular intoxication induces DNA damage and activation of the DNA damage responses, which results in arrest of the target cells in the G1 and/or G2 phases of the cell cycle and activation of DNA repair mechanisms. Cells that fail to repair the damage will senesce or undergo apoptosis. This review will focus on the well-characterized aspects of the CDT biology and discuss the questions that still remain unanswered.
authors: Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden, Box 285, S-171 77 Stockholm, Sweden. lina.guerra@ki.se
authors: Lina
authors: L
authors: Guerra
authors: Ximena
authors: X
authors: Cortes-Bratti
authors: Riccardo
authors: R
authors: Guidi
authors: Teresa
authors: T
authors: Frisan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001427:Bacterial Toxins / Q000737:chemistry / Q000235:genetics / Q000633:toxicity*; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D003092:Colitis / Q000209:etiology / Q000276:immunology / Q000382:microbiology; D004249:DNA Damage; D004705:Endocytosis / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000378:metabolism / Q000472:pathogenicity; D006801:Humans; D009369:Neoplasms / Q000209:etiology / Q000276:immunology / Q000382:microbiology; D010518:Periodontitis / Q000209:etiology / Q000276:immunology / Q000382:microbiology; D011485:Protein Binding; D021122:Protein Subunits; D037521:Virulence Factors / Q000737:chemistry / Q000235:genetics / Q000633:toxicity
chemical_list: D001427:Bacterial Toxins; D021122:Protein Subunits; D037521:Virulence Factors; C067044:cytolethal distending toxin