GenomeRNAi - a database for RNAi phenotypes and reagents
TitleScreen TitleAssayBiomodelSpecies
HIF-1α is involved in mediating apoptosis resistance to Chlamydia trachomatis-infected cells. Sharma et al. (2011) Apoptosis regulation after Chlamydia trachomatis serovar L2 infection Cleaved cytokeratin-18 protein expressionHeLaH. sapiens

Abstract

Chlamydiae are obligate intracellular Gram-negative bacteria that cause widespread diseases in humans. Due to the intimate association between bacterium and host, Chlamydia evolved various strategies to protect their host cell against death-inducing stimuli, allowing the bacterium to complete its development cycle. An RNA interference (RNAi)-based screen was used to identify host cell factors required for apoptosis resistance of human epithelial cells infected with Chlamydia trachomatis serovar L2. Among the 32 validated hits, the anti-apoptotic Bcl-2 family member Mcl-1 was identified as a target. Protein network analyses implicated the transcription factor hypoxia-induced factor 1 alpha (HIF-1α) to be central to the regulation of many of the identified targets. Further mechanistic investigations showed that HIF-1α was stabilized within the host cell cytoplasm during early infection time points, followed by its translocation to the nucleus and eventual transcriptional activation of Mcl-1. siRNA-mediated depletion of HIF-1α led to a drastic decrease in Mcl-1, rendering the cell sensitive to apoptosis induction. Taken together, our findings identify HIF-1α as responsible for upregulation of Mcl-1 and the maintenance of apoptosis resistance during Chlamydia infection.

Screen details


Stable Id: GR00206-A
Screen title: Apoptosis regulation after Chlamydia trachomatis serovar L2 infection
Assay: Cleaved cytokeratin-18 protein expression
Method: Fluorescence
Scope: Apoptosis, cellular trafficking and cell signalling genes
Screen type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: HeLa
Library: Custom-made, Custom-made
Reagent type: siRNA
Score type: p-value
Cutoff: <= 0.05
Notes: Author-reviewed data