Mcl-1 is a key regulator of apoptosis resistance in Chlamydia trachomatis-infected cells.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 18769617.
- Also identified by DOI 10.1371/journal.pone.0003102 and PMC identifier 2518856.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Chlamydia are obligate intracellular bacteria that cause variety of human diseases. Host cells infected with Chlamydia are protected against many different apoptotic stimuli. The induction of apoptosis resistance is thought to be an important immune escape mechanism allowing Chlamydia to replicate inside the host cell. Infection with C. trachomatis activates the Raf/MEK/ERK pathway and the PI3K/AKT pathway. Here we show that inhibition of these two pathways by chemical inhibitors sensitized C. trachomatis infected cells to granzyme B-mediated cell death. Infection leads to the Raf/MEK/ERK-mediated up-regulation and PI3K-dependent stabilization of the anti-apoptotic Bcl-2 family member Mcl-1. Consistently, interfering with Mcl-1 up-regulation sensitized infected cells for apoptosis induced via the TNF receptor, DNA damage, granzyme B and stress. Our data suggest that Mcl-1 up-regulation is primarily required to maintain apoptosis resistance in C. trachomatis-infected cells.
Medical subject headings
- Apoptosis
- Chlamydia Infections
- Chlamydia trachomatis
- Gene Expression Regulation, Bacterial
- Proto-Oncogene Proteins c-bcl-2