Journal article
Bacterial genotoxin triggers FEN1-dependent RhoA activation, cytoskeleton remodeling and cell survival
Journal of cell science, Vol.124(16), pp.2735-2742
08/15/2011
DOI: 10.1242/jcs.085845
PMID: 21807938
Abstract
The DNA damage response triggered by bacterial cytolethal distending toxins (CDTs) is associated with activation of the actin-regulating protein RhoA and phosphorylation of the downstream-regulated mitogen-activated protein kinase (MAPK) p38, which promotes the survival of intoxicated (i.e. cells exposed to a bacterial toxin) cells. To identify the effectors of this CDT-induced survival response, we screened a library of 4492 Saccharomyces cerevisiae mutants that carry deletions in nonessential genes for reduced growth following inducible expression of CdtB. We identified 78 genes whose deletion confers hypersensitivity to toxin. Bioinformatics analysis revealed that DNA repair and endocytosis were the two most overrepresented signaling pathways. Among the human orthologs present in our data set, FEN1 and TSG101 regulate DNA repair and endocytosis, respectively, and also share common interacting partners with RhoA. We further demonstrate that FEN1, but not TSG101, regulates cell survival, MAPK p38 phosphorylation, RhoA activation and actin cytoskeleton reorganization in response to DNA damage. Our data reveal a previously unrecognized crosstalk between DNA damage and cytoskeleton dynamics in the regulation of cell survival, and might provide new insights on the role of chronic bacteria infection in carcinogenesis.
Details
- Title: Subtitle
- Bacterial genotoxin triggers FEN1-dependent RhoA activation, cytoskeleton remodeling and cell survival
- Creators
- Lina Guerra - Karolinska InstitutetRiccardo Guidi - Karolinska InstitutetIlse Slot - Karolinska InstitutetSimone Callegari - Karolinska InstitutetRamakrishna Sompallae - Karolinska InstitutetCarol L. Pickett - Albert B. Chandler HospitalStefan Astrom - Stockholm UniversityFrederik Eisele - University of StuttgartDieter Wolf - University of StuttgartCamilla Sjogren - Karolinska InstitutetMaria G. Masucci - Karolinska InstitutetTeresa Frisan - Karolinska Institutet
- Resource Type
- Journal article
- Publication Details
- Journal of cell science, Vol.124(16), pp.2735-2742
- Publisher
- Company Biologists Ltd
- DOI
- 10.1242/jcs.085845
- PMID
- 21807938
- ISSN
- 0021-9533
- eISSN
- 1477-9137
- Number of pages
- 8
- Grant note
- Swedish Cancer Society LSHC-CT-2005-018704 / European Community Ake-Wiberg Foundation Karolinska Institutet Robert Lundberg Memorial Fundation Swedish Research Council Magnus Bergvall Fundation
- Language
- English
- Date published
- 08/15/2011
- Academic Unit
- Pathology
- Record Identifier
- 9984622056802771
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