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          Institute: MPI für Infektionsbiologie     Collection: Department of Molecular Biology     Display Documents



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ID: 439759.0, MPI für Infektionsbiologie / Department of Molecular Biology
Bim and Bmf Synergize To Induce Apoptosis in Neisseria Gonorrhoeae Infection
Authors:Kepp, Oliver; Gottschalk, Kathleen; Churin, Yuri; Rajalingam, Krishnaraj; Brinkmann, Volker; Machuy, Nikolaus; Kroemer, Guido; Rudel, Thomas
Language:English
Date of Publication (YYYY-MM-DD):2009-03
Title of Journal:PLoS Pathogens
Volume:5
Issue / Number:3
Sequence Number of Article:e1000348
Copyright:© 2009 Kepp et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Review Status:Peer-review
Audience:Experts Only
Abstract / Description:Bcl-2 family proteins including the pro-apoptotic BH3-only proteins are central regulators of apoptotic cell death. Here we show by a focused siRNA miniscreen that the synergistic action of the BH3-only proteins Bim and Bmf is required for apoptosis induced by infection with Neisseria gonorrhoeae (Ngo). While Bim and Bmf were associated with the cytoskeleton of healthy cells, they both were released upon Ngo infection. Loss of Bim and Bmf from the cytoskeleton fraction required the activation of Jun-N-terminal kinase-1 (JNK-1), which in turn depended on Rac-1. Depletion and inhibition of Rac-1, JNK-1, Bim, or Bmf prevented the activation of Bak and Bax and the subsequent activation of caspases. Apoptosis could be reconstituted in Bim-depleted and Bmf-depleted cells by additional silencing of antiapoptotic Mcl-1 and Bcl-X-L, respectively. Our data indicate a synergistic role for both cytoskeletal-associated BH3-only proteins, Bim, and Bmf, in an apoptotic pathway leading to the clearance of Ngo-infected cells.
Free Keywords:MITOCHONDRIAL-MEMBRANE PERMEABILIZATION; INDUCED CELL-DEATH;; FACTOR-KAPPA-B; EPITHELIAL-CELLS; BCL-2 FAMILY; INFLAMMATORY CYTOKINES;; DEPENDENT APOPTOSIS; ACTIVATOR PROTEIN-1; MOTOR COMPLEX; BAX
External Publication Status:published
Document Type:Article
Communicated by:Hilmar Fünning
Affiliations:MPI für Infektionsbiologie/Department of Molecular Biology
External Affiliations:INSERM, U848, Institute Gustave Roussy, Université Paris Sud, Paris, France; Biozentrum, University of Würzburg, Department of Microbiology, Würzburg, Germany.
Identifiers:ISSN:1553-7366 %R e1000348 10.1371/journal.ppat.1000348 [ID No:1]
ISI:000266216000027 [ID No:2]
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