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.

journal_name

PLoS Pathog

journal_title

PLoS pathogens

authors

Rajalingam K,Sharma M,Paland N,Hurwitz R,Thieck O,Oswald M,Machuy N,Rudel T

doi

10.1371/journal.ppat.0020114

subject

Has Abstract

pub_date

2006-10-01 00:00:00

pages

e114

issue

10

eissn

1553-7366

issn

1553-7374

pii

06-PLPA-RA-0202R2

journal_volume

2

pub_type

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