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| Item Type: | Article |
|---|---|
| Title: | Chlamydia infection depends on a functional MDM2-p53 axis |
| Creators Name: | Gonzalez, E., Rother, M., Kerr, M.C., Al-Zeer, M.A., Abu-Lubad, M., Kessler, M., Brinkmann, V., Loewer, A. and Meyer, T.F. |
| Abstract: | Chlamydia, a major human bacterial pathogen, assumes effective strategies to protect infected cells against death-inducing stimuli, thereby ensuring completion of its developmental cycle. Paired with its capacity to cause extensive host DNA damage, this poses a potential risk of malignant transformation, consistent with circumstantial epidemiological evidence. Here we reveal a dramatic depletion of p53, a tumor suppressor deregulated in many cancers, during Chlamydia infection. Using biochemical approaches and live imaging of individual cells, we demonstrate that p53 diminution requires phosphorylation of Murine Double Minute 2 (MDM2; a ubiquitin ligase) and subsequent interaction of phospho-MDM2 with p53 before induced proteasomal degradation. Strikingly, inhibition of the p53-MDM2 interaction is sufficient to disrupt intracellular development of Chlamydia and interferes with the pathogen's anti-apoptotic effect on host cells. This highlights the dependency of the pathogen on a functional MDM2-p53 axis and lends support to a potentially pro-carcinogenic effect of chlamydial infection. |
| Keywords: | Apoptosis, Chlamydia, Chlamydia Infections, Chlamydia trachomatis, HeLa Cells, Neoplastic Cell Transformation, Phosphorylation, Proto-Oncogene Proteins c-mdm2, Tumor Suppressor Protein p53, Western Blotting |
| Source: | Nature Communications |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Volume: | 5 |
| Page Range: | 5201 |
| Date: | 13 November 2014 |
| Official Publication: | https://doi.org/10.1038/ncomms6201 |
| PubMed: | View item in PubMed |
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