González, Erik ; Rother, Marion ; Kerr, Markus C. ; Al-Zeer, Munir A. ; Abu-Lubad, Mohammad ; Kessler, Mirjana ; Brinkmann, Volker ; Loewer, Alexander ; Meyer, Thomas F. (2014)
Chlamydia infection depends on a functional MDM2-p53 axis.
In: Nature communications, 5
Artikel, Bibliographie
Kurzbeschreibung (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.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2014 |
| Autor(en): | González, Erik ; Rother, Marion ; Kerr, Markus C. ; Al-Zeer, Munir A. ; Abu-Lubad, Mohammad ; Kessler, Mirjana ; Brinkmann, Volker ; Loewer, Alexander ; Meyer, Thomas F. |
| Art des Eintrags: | Bibliographie |
| Titel: | Chlamydia infection depends on a functional MDM2-p53 axis. |
| Sprache: | Englisch |
| Publikationsjahr: | 2014 |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | Nature communications |
| Jahrgang/Volume einer Zeitschrift: | 5 |
| Kurzbeschreibung (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. |
| Fachbereich(e)/-gebiet(e): | 10 Fachbereich Biologie 10 Fachbereich Biologie > Systems Biology of the Stress Response |
| Hinterlegungsdatum: | 02 Sep 2015 08:27 |
| Letzte Änderung: | 02 Sep 2015 08:27 |
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