IAP-IAP Complexes Required for Apoptosis Resistance of C. trachomatis–Infected Cells

PLoS Pathogens

Robert Hurwitz¹  Manu Sharma²  Nicole Paland²  Monique Oswald²  Nikolaus Machuy²  Oliver Thieck²  Krishnaraj Rajalingam²  Thomas Rudel² 

[1] Biochemistry/Protein Purification Core Facility, Max Planck Institute for Infection Biology, Berlin, Germany;Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin, Germany

关键词: Apoptosis;    Chlamydia infection;    Small interfering RNAs;    HeLa cells;    Immunoblot analysis;    Gel filtration;    Host cells;    Immunoblotting;   

DOI  :  10.1371/journal.ppat.0020114

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY