title: IAP-IAP complexes required for apoptosis resistance of C. trachomatis-infected cells.
abstract: 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.
authors.affiliation: Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Krishnaraj
authors.initials: K
authors.lastname: Rajalingam
authors.forename: Manu
authors.initials: M
authors.lastname: Sharma
authors.forename: Nicole
authors.initials: N
authors.lastname: Paland
authors.forename: Robert
authors.initials: R
authors.lastname: Hurwitz
authors.forename: Oliver
authors.initials: O
authors.lastname: Thieck
authors.forename: Monique
authors.initials: M
authors.lastname: Oswald
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Machuy
authors.forename: Thomas
authors.initials: T
authors.lastname: Rudel
mesh_terms: D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002690:Chlamydia Infections / Q000503:physiopathology; D002692:Chlamydia trachomatis / Q000254:growth & development* / Q000472:pathogenicity / Q000502:physiology; D004847:Epithelial Cells / Q000378:metabolism* / Q000382:microbiology* / Q000473:pathology; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism*; D019169:Jurkat Cells; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D051034:Inhibitor of Apoptosis Proteins; D046912:Multiprotein Complexes; D034741:RNA, Small Interfering; D018124:Receptors, Tumor Necrosis Factor; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D053148:Caspase 3