Bcl-2 antiapoptotic protein mediates verotoxin II–induced cell death: possible association between Bcl-2 and tissue failure by <i>E. coli</i> O157:H7
Genes & DevelopmentPublished 15 July 2000Open access
Atsushi Suzuki, Hirofumi Doi, Fumiko Matsuzawa, Sei‐ichi Aikawa, Kyoko Takiguchi, Hirokazu Kawano
Citations45
SJR quartileQ1
SJR score4.00
SNIP1.43
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
It is proposed that Bcl-2 mediates VTII-induced target cell death by the interaction with each pentameric sequence of BH1 domain.
Abstract
Verotoxin II (VTII: or Shiga-like toxin 2) is a key factor for Escherichia coli O157:H7-induced multiple tissue failure and contains a pentameric sequence (NWGRI) similar to the Bcl-2 homolog domain, BH1. In the current study, we demonstrate that VTII, but not VTI, interacts with Bcl-2 through each BH1 domain pentameric sequence (NWGRI) and that the VTII/Bcl-2 complex is necessary for cell-death induction in target cells. VTII translocates to mitochondria and induces cell death only when target cells are expressing Bcl-2. In addition, interruption of VTII-Bcl-2 complex formation by a pentameric BH1 synthetic peptide suppresses VTII-induced cell death. In the present article, we propose that Bcl-2 mediates VTII-induced target cell death by the interaction with each pentameric sequence of BH1 domain.
Keywords
Immunology and MicrobiologyBiochemistry, Genetics and Molecular Biology
International review of cytologyCell Death: The Significance of Apoptosis
7,223 Citations1980A H Wyllie, J. F. R. Kerr +1 more
It has proved feasible to categorize most if not all dying cells into one or the other of two discrete and distinctive patterns of morphological change, which have, generally, been found to occur under disparate but individually characteristic circumstances.
CellBcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programed cell death
6,013 Citations1993Zoltán N. Oltval, Curt Milliman +1 more
Overexpressed Bax accelerates apoptotic death induced by cytokine deprivation in an IL-3-dependent cell line and counters the death repressor activity of B cl-2, suggesting a model in which the ratio of Bcl-2 to Bax determines survival or death following an apoptotic stimulus.
CellApoptosis by Death Factor
4,990 Citations1997Shigekazu Nagata
This work was supported in part by Grants-in-Aid from the Ministry of Education, Science, and Culture of Japan and by a Research Grant from the Princess Takamatsu Cancer Research Fund, and performed in part through Special Coordination Funds of the Science and Technology Agency of the Japanese Government.
SciencePrevention of Apoptosis by Bcl-2: Release of Cytochrome c from Mitochondria Blocked
4,943 Citations1997Jie Yang, Xuesong Liu +7 more
One possible role of Bcl-2 in prevention of apoptosis is to block cytochrome c release from mitochondria, which is normally located in the mitochondrial intermembrane space.
ScienceThe Fas Death Factor
4,022 Citations1995Shigekazu Nagata, Pierre Golstein
Fas ligand (FasL), a cell surface molecule belonging to the tumor necrosis factor family, binds to its receptor Fas, thus inducing apoptosis of Fas-bearing cells.
NatureBcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells
3,229 Citations1988David L. Vaux, Suzanne Cory +1 more
Results argue that bcl-2 provided a distinct survival signal to the cell and may contribute to neoplasia by allowing a clone to persist until other oncogenes, such as c-myc, become activated.
NatureA caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD
3,182 Citations1998Masato Enari, Hideki Sakahira +4 more
A caspase-activated deoxyribonuclease (CAD) and its inhibitor (ICAD) have now been identified in the cytoplasmic fraction of mouse lymphoma cells and seems to function as a chaperone for CAD during its synthesis, remaining complexed with CAD to inhibit its DNase activity.
CellApaf-1, a Human Protein Homologous to C. elegans CED-4, Participates in Cytochrome c–Dependent Activation of Caspase-3
3,146 Citations1997Hua Zou, William J. Henzel +3 more
The purification and cDNA cloning of Apaf-1, a novel 130 kd protein from HeLa cell cytosol that participates in the cytochrome c-dependent activation of caspase-3, leading to apoptosis is reported here.
Cellbcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death
3,113 Citations1993Lawrence Boise, Maribel González‐García +7 more
Data suggest that bcl-x plays an important role in both positive and negative regulation of programmed cell death, as well as in tissues containing long-lived postmitotic cells, such as adult brain.
NatureCleavage of poly(ADP-ribose) polymerase by a proteinase with properties like ICE
2,576 Citations1994Yuri Lazebnik, Scott H. Kaufmann +3 more
A novel protease resembling ICE (prICE) that is active in a cell-free system that reproduces the morphological and biochemical events of apoptosis in the extracts including morphological changes, cleavage of PARP and production of an oligonucleosomal ladder.
CellHuman ICE/CED-3 Protease Nomenclature
2,381 Citations1996Emad S. Alnemri, David J. Livingston +5 more
A committee of several scientists who have been involved in the identification and characterization of these enzymes have formed a committee, with the objective of proposing a nomenclature for the human members of this protease family that is sensible and easy to use.
NatureBcl-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC
2,171 Citations1999Shigeomi Shimizu, Masashi Narita +2 more
The results indicate that the Bcl-2 family of proteins bind to the VDAC in order to regulate the mitochondrial membrane potential and the release of cytochrome c during apoptosis.
ScienceCloning of the Chromosome Breakpoint of Neoplastic B Cells with the t(14;18) Chromosome Translocation
1,781 Citations1984Yoshihide Tsujimoto, L R Finger +3 more
A DNA probe obtained appears to identify bcl-2, a gene locus on chromosome 18 (band q21) that is unrelated to known oncogenes and may be important in the pathogenesis of B-cell neoplasms with this translocation.
CellBcl-2-deficient mice demonstrate fulminant lymphoid apoptosis, polycystic kidneys, and hypopigmented hair
1,634 Citations1993Deborah J. Veis, Christine M. Sorenson +2 more
Bcl-2-/-mice complete embryonic development, but display growth retardation and early mortality postnatally, and turn gray with the second hair follicle cycle, implicating a defect in redox-regulated melanin synthesis.
Clinical Microbiology ReviewsPathogenesis and Diagnosis of Shiga Toxin-Producing <i>Escherichia coli</i> Infections
1,416 Citations1998James C. Paton, Adrienne W. Paton
Increased application of advanced molecular technologies in clinical laboratories has significantly improved the capacity to diagnose STEC infection early in the course of disease and to detect low levels of environmental contamination, creating a potential window of opportunity for future therapeutic intervention.
The Journal of Experimental MedicineA cell-killing monoclonal antibody (anti-Fas) to a cell surface antigen co-downregulated with the receptor of tumor necrosis factor.
1,416 Citations1989Shin Yonehara, A Ishii +1 more
It is suggested that the cell-killing activity of TNF is mediated by Fas antigen associated with the TNF-R, an mAb specific for a human cell surface component (termed anti-Fas mAb).
NatureBH1 and BH2 domains of Bcl-2 are required for inhibition of apoptosis and heterodimerization with Bax
1,329 Citations1994Xiao-Ming Yin, Zoltán N. Oltvai +1 more
Results establish a functional role for the BH1 and BH2 domains and suggest Bcl-2 exerts its action through heterodimerization with Bax, yet still permitted B cl-2 homo-dimerization.
NatureSequential activation of ICE-like and CPP32-like proteases during Fas-mediated apoptosis
982 Citations1996Masato Enari, Robert V. Talanian +2 more
It is shown that Fas sequentially activates ICE- and CPP32-like proteases, and that downstream CPP 32, together with a component(s) in the cytoplasm, causes apoptosis of nuclei.
Genes & DevelopmentBID: a novel BH3 domain-only death agonist.
962 Citations1996Kai Wang, Xiaoming Yin +3 more
This work used interactive cloning to identify Bid, which encodes a novel death agonist that heterodimerizes with either agonists (BAX) or antagonists (BCL-2), and favors a model in which BID represents a death ligand for the membrane-bound receptor BAX.
CellMolecular regulation of apoptosis: Genetic controls on cell death
914 Citations1993Gwyn T. Williams, Christopher A. Smith
It is now widely accepted that apoptosis is a genedirected process and can be seen, alongside more familiar gene-directed processes like differentiation, as part of the repertoire available to the cell to respond to external and internal stimuli.
NatureInduction of apoptosis by the Bcl-2 homologue Bak
734 Citations1995Thomas W. Chittenden, Elizabeth A. Harrington +5 more
The complementary DNA cloning and functional analysis of a new Bcl-2 homologue, Bak, is described, which promotes cell death and counteracts the protection from apoptosis provided by B cl-2.
The EMBO JournalAlternative promoters and exons, somatic mutation and deregulation of the Bcl‐2‐Ig fusion gene in lymphoma.
494 Citations1988M Seto, Ulrich Jaeger +5 more
The most common translocation in human lymphoma, the t(14;18)(q32;q21), generates heterogeneous 4.2‐7.2 kb Bcl‐2‐immunoglobulin (Ig) chimeric mRNAs resulting from alternative B cl‐2 5′ exons and varied Ig 3′ untranslated regions (UT).
The EMBO JournalA conserved domain in Bak, distinct from BH1 and BH2, mediates cell death and protein binding functions.
492 Citations1995Thomas W. Chittenden, Cathy Flemington +6 more
A domain is identified in Bak that is both necessary and sufficient for cytotoxic activity and binding to Bcl‐xL, which is of central importance in mediating the function of multiple cell death‐regulatory proteins that interact with B cl‐2 family members.
NatureAcinus is a caspase-3-activated protein required for apoptotic chromatin condensation
433 Citations1999Setsuko Sahara, Mamoru Aoto +4 more
An in vitro system is used to identify a new nuclear factor, designated Acinus, which induces apoptotic chromatin condensation after cleavage by caspase-3 without inducing DNA fragmentation.
Infection and ImmunityComparison of the relative toxicities of Shiga-like toxins type I and type II for mice
386 Citations1993Vernon L. Tesh, J A Burris +5 more
Data suggest that structural/functional differences between the two toxins, possibly involving holotoxin stability and/or receptor affinity, may contribute to the differential LD50s in mice.
OncogeneResistance to Fas-mediated apoptosis: activation of Caspase 3 is regulated by cell cycle regulator p21WAF1 and IAP gene family ILP
351 Citations1998Atsushi Suzuki, Yumi Tsutomi +3 more
It is reported that caspase 3 inactivation for the resistance to Fas-mediated apoptosis is induced by a procaspase3/p21 complex formation and direct inhibition of activated caspases 3 by ILP.
PubMedMultiple subcellular localization of bcl-2: detection in nuclear outer membrane, endoplasmic reticulum membrane, and mitochondrial membranes.
284 Citations1994Yukihiro Akao, Yuki Otsuki +3 more
The use of biochemical fractionation, immunofluorescence laser-scanning confocal microscopy, and immunoelectron microscopy with mouse anti-human bcl-2 monoclonal antibody revealed the protein prominently in the nuclear envelope, endoplasmic reticulum membrane, and mitochondrial membranes, suggesting an important role for this protein in several different membrane compartments.
PubMedApoptosis induced in Burkitt's lymphoma cells via Gb3/CD77, a glycolipid antigen.
236 Citations1993Marianne Mangeney, Clifford A. Lingwood +4 more
It is shown that verotoxin, also called Shiga-like toxin, induces cell death in Gb3/CD77(+) Burkitt's lymphoma cells, not only by inhibiting protein synthesis as classically described but also through an additional mechanism, namely apoptosis.
PubMedbcl-2 deficiency in mice leads to pleiotropic abnormalities: accelerated lymphoid cell death in thymus and spleen, polycystic kidney, hair hypopigmentation, and distorted small intestine.
229 Citations1995Shinji Kamada, Akihiko Shimono +7 more
The authors' bcl-2-/- mice revealed novel defects in the small intestine, characterized by retarded development, accelerated exfoliation of epithelial cells, and very few mitotic progenitor cells.
PubMedStress-resistance conferred by high level of bcl-2 alpha protein in human B lymphoblastoid cell.
220 Citations1989Yoshihide Tsujimoto
The improved survival of cells as a result of high levels of the bcl-2 alpha protein is not specific to the absence of growth factor but is found to occur with a variety of stresses.
PubMedInvolvement of CPP32/Yama(-like) proteases in Fas-mediated apoptosis.
164 Citations1996Junichi Hasegawa, Shinji Kamada +5 more
Fas-mediated apoptosis is inhibited by the CPP32/Yama inhibitor DEVD- CHO, but not by the ICE inhibitor YVAD-CHO, suggesting a dominant role for the C PP32/ Yama(-like) proteases and not ICE itself in Fas-mediated euthanasia of the human carcinoma cell lines.
Molecular and Cellular BiologyMitochondrial Regulation of Cell Death: Mitochondria Are Essential for Procaspase 3-p21 Complex Formation To Resist Fas-Mediated Cell Death
129 Citations1999Atsushi Suzuki, Yumi Tsutomi +3 more
It is concluded that mitochondria are necessary for procaspase 3-p21 complex formation and proposed that the mitochondrial role during cell death is not only death induction but also death suppression.
PubMedShiga-like toxin-1 receptor on human breast cancer, lymphoma, and myeloma and absence from CD34(+) hematopoietic stem cells: implications for ex vivo tumor purging and autologous stem cell transplantation.
101 Citations1999EC LaCasse, Mark R. Bray +14 more
The results suggest the ex vivo use of SLT-1 in purging SLt-1 receptor-expressing malignant cells from autologous stem cell grafts of breast cancer, lymphoma, and myeloma patients.
Proceedings of the National Academy of SciencesAlteration of the carbohydrate binding specificity of verotoxins from Gal alpha 1-4Gal to GalNAc beta 1-3Gal alpha 1-4Gal and vice versa by site-directed mutagenesis of the binding subunit.
74 Citations1992Gregory J. Tyrrell, K. Ramotar +4 more
Both wild-type VTE and GT3 were purified to homogeneity and binding kinetics in vitro were determined with purified GSLs from human kidney, and the cell cytotoxicity spectrum of the mutant toxin was also found to be altered in comparison with VTE.
Journal of Neuro-OncologyVerotoxins inhibit the growth of and induce apoptosis in human astrocytoma cells
62 Citations1998Sara Arab, Masaji Murakami +6 more
It is indicated that verotoxin/Gb3 targetting may provide a novel basis for the inhibition of astrocytoma tumour cell growth, and the anti-cancer spectrum of activity of VT to human brain tumors is extended.
Journal of the American Society of NephrologyVerocytotoxin inhibits mitogenesis and protein synthesis in purified human glomerular mesangial cells without affecting cell viability
57 Citations1997P.A. van Setten, V W van Hinsbergh +6 more
Although protein synthesis was inhibited in mesangial cells, all cells remained viable, both under basal and tumor necrosis factor-alpha-stimulated conditions, suggesting that the marked reduction in protein synthesis may impair a proper response of the cells in conditions of increased demand of newly synthesized proteins.
Veterinary MicrobiologyCharacteristics of the Shiga-like toxin produced by Escherichia coli associated with porcine edema disease
43 Citations1990Victor P. J. Gannon, Carlton Gyles
SLT-IIv and SLT-HI8 had lower cytotoxic titers on HeLa cells compared with Vero cells and were more active on MDBK cells than were the other SLTs.
ToxiconThe RNA-N-glycosidase activity of Shiga-like toxin I: Kinetic parameters of the native and activated toxin
29 Citations1997Maurizio Brigotti, Domenica Carnicelli +4 more
The kinetic constants of the adenine release from highly purified Artemia salina ribosomes catalysed by Shiga-like toxin I and by its A subunit before and after treatment with trypsin, urea and dithiothreitol or urea
Advances in experimental medicine and biologyIntracellular Transport and Processing of Protein Toxins Produced by Enteric Bacteria
17 Citations1997Kirsten Sandvig, Oslo Garred +1 more
Intracellular transport and processing of a few of the protein toxins produced by enteric bacteria, namely Clostridium difficile toxin A and B, cholera toxin and the related heat-labile toxin produced by Escherichia coli, and Shiga toxin and Shigo-like toxins are presented.