IAP-IAP complexes required for apoptosis resistance of C. trachomatis-infected cells
- Host cells infected with obligate intracellular bacteria Chlamydia trachomatis are profoundly resistant to diverse apoptotic stimuli. The molecular mechanisms underlying the block in apoptotic signaling of infected cells is not well understood. Here we investigated the molecular mechanism by which apoptosis induced via the tumor necrosis factor (TNF) receptor is prevented in infected epithelial cells. Infection with C. trachomatis leads to the up-regulation of cellular inhibitor of apoptosis (cIAP)-2, and interfering with cIAP-2 up-regulation sensitized infected cells for TNF-induced apoptosis. Interestingly, besides cIAP-2, cIAP-1 and X-linked IAP, although not differentially regulated by infection, are required to maintain apoptosis resistance in infected cells. We detected that IAPs are constitutively organized in heteromeric complexes and small interfering RNA-mediated silencing of one of these IAPs affects the stability of another IAP. In particular, the stability of cIAP-2 is modulated by the presence of X-linked IAP and their interaction is stabilized in infected cells. Our observations suggest that IAPs are functional and stable as heteromers, a thus far undiscovered mechanism of IAP regulation and its role in modulation of apoptosis.
| Author: | Krishnaraj RajalingamORCiDGND, Manu Sharma, Nicole Paland, Robert Hurwitz, Oliver Thieck, Monique Oswald, Nikolaus Machuy, Thomas Rudel |
|---|---|
| URN: | urn:nbn:de:hebis:30:3-272392 |
| DOI: | https://doi.org/10.1371/journal.ppat.0020114 |
| ISSN: | 1553-7374 |
| ISSN: | 1553-7366 |
| Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/17069460 |
| Parent Title (English): | PLoS pathogens |
| Publisher: | PLoS |
| Place of publication: | Lawrence, Kan. |
| Document Type: | Article |
| Language: | English |
| Date of Publication (online): | 2006/10/27 |
| Date of first Publication: | 2006/10/27 |
| Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
| Release Date: | 2013/02/22 |
| Volume: | 2 |
| Issue: | (10): e114 |
| Page Number: | 11 |
| First Page: | 1013 |
| Last Page: | 1023 |
| Note: | Copyright: © 2006 Rajalingam 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. |
| HeBIS-PPN: | 33204890X |
| Institutes: | Biochemie, Chemie und Pharmazie / Biochemie und Chemie |
| Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
| Sammlungen: | Universitätspublikationen |
| Sammlung Biologie / Sondersammelgebiets-Volltexte | |
| Licence (German): |  Creative Commons - Namensnennung 3.0 |
