Document Detail


Bim and Bmf synergize to induce apoptosis in Neisseria gonorrhoeae infection.
MedLine Citation:
PMID:  19300516     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Oliver Kepp; Kathleen Gottschalk; Yuri Churin; Krishnaraj Rajalingam; Volker Brinkmann; Nikolaus Machuy; Guido Kroemer; Thomas Rudel
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-03-20
Journal Detail:
Title:  PLoS pathogens     Volume:  5     ISSN:  1553-7374     ISO Abbreviation:  PLoS Pathog.     Publication Date:  2009 Mar 
Date Detail:
Created Date:  2009-03-20     Completed Date:  2009-05-12     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  101238921     Medline TA:  PLoS Pathog     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e1000348     Citation Subset:  IM    
Affiliation:
Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin, Germany.
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MeSH Terms
Descriptor/Qualifier:
Adaptor Proteins, Signal Transducing / metabolism*
Apoptosis / physiology*
Apoptosis Regulatory Proteins / metabolism*
Blotting, Western
Cell Adhesion / physiology
Cytoskeleton / ultrastructure
Flow Cytometry
Fluorescent Antibody Technique
Gonorrhea / metabolism*,  pathology
Hela Cells
Humans
Immunoprecipitation
Membrane Proteins / metabolism*
Microscopy, Electron, Transmission
Mitogen-Activated Protein Kinase 8 / metabolism
Neisseria gonorrhoeae / physiology
Proto-Oncogene Proteins / metabolism*
RNA, Small Interfering
Signal Transduction / physiology*
rac GTP-Binding Proteins / metabolism
Chemical
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/Apoptosis Regulatory Proteins; 0/BMF protein, human; 0/Bcl-2-like protein 11; 0/Membrane Proteins; 0/Proto-Oncogene Proteins; 0/RNA, Small Interfering; EC 2.7.11.24/Mitogen-Activated Protein Kinase 8; EC 3.6.5.2/rac GTP-Binding Proteins
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