TU Darmstadt / ULB / TUbiblio

Chlamydia infection depends on a functional MDM2-p53 axis.

González, Erik ; Rother, Marion ; Kerr, Markus C. ; Al-Zeer, Munir A. ; Abu-Lubad, Mohammad ; Kessler, Mirjana ; Brinkmann, Volker ; Loewer, Alexander ; Meyer, Thomas F. :
Chlamydia infection depends on a functional MDM2-p53 axis.
In: Nature communications, 5 p. 5201. ISSN 2041-1723
[Artikel], (2014)

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.
Titel: Chlamydia infection depends on a functional MDM2-p53 axis.
Sprache: Englisch
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.

Titel der Zeitschrift, Zeitung oder Schriftenreihe: Nature communications
Band: 5
Fachbereich(e)/-gebiet(e): Fachbereich Biologie, Biology
Fachbereich Biologie, Biology > Molekularbiologie der Stressantwort
Hinterlegungsdatum: 02 Sep 2015 08:27
Export:

Optionen (nur für Redakteure)

Eintrag anzeigen Eintrag anzeigen