Tumor Suppressor p53 Alters Host Cell Metabolism to Limit Chlamydia trachomatis Infection
Zitieren Sie bitte immer diese URN: urn:nbn:de:bvb:20-opus-118200
- Obligate intracellular bacteria depend entirely on nutrients from the host cell for their reproduction. Here, we show that obligate intracellular Chlamydia downregulate the central tumor suppressor p53 in human cells. This reduction of p53 levels is mediated by the PI3K-Akt signaling pathway, activation of HDM2, and subsequent proteasomal degradation of p53. The stabilization of p53 in human cells severely impaired chlamydial development and caused the loss of infectious particle formation. DNA-damage-induced p53 interfered with chlamydialObligate intracellular bacteria depend entirely on nutrients from the host cell for their reproduction. Here, we show that obligate intracellular Chlamydia downregulate the central tumor suppressor p53 in human cells. This reduction of p53 levels is mediated by the PI3K-Akt signaling pathway, activation of HDM2, and subsequent proteasomal degradation of p53. The stabilization of p53 in human cells severely impaired chlamydial development and caused the loss of infectious particle formation. DNA-damage-induced p53 interfered with chlamydial development through downregulation of the pentose phosphate pathway (PPP). Increased expression of the PPP key enzyme glucose-6-phosphate dehydrogenase rescued the inhibition of chlamydial growth induced by DNA damage or stabilized p53. Thus, downregulation of p53 is a key event in the chlamydial life cycle that reprograms the host cell to create a metabolic environment supportive of chlamydial growth.…
Autor(en): | Christine Siegl, Bhupesh K. Prusty, Karthika Karunakaran, Jörg Wischhusen, Thomas Rudel |
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URN: | urn:nbn:de:bvb:20-opus-118200 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Fakultät für Biologie / Theodor-Boveri-Institut für Biowissenschaften |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | Cell Reports |
ISSN: | 2211-1247 |
Erscheinungsjahr: | 2014 |
Band / Jahrgang: | 9 |
Heft / Ausgabe: | 3 |
Seitenangabe: | 918–929 |
Originalveröffentlichung / Quelle: | Cell Reports 9, 918–929. DOI:10.1016/j.celrep.2014.10.004 |
DOI: | https://doi.org/10.1016/j.celrep.2014.10.004 |
PubMed-ID: | https://pubmed.ncbi.nlm.nih.gov/25437549 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Freie Schlagwort(e): | chlamydia trachomatis; tumor |
Datum der Freischaltung: | 04.09.2015 |
Lizenz (Deutsch): | CC BY-NC-ND: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell, Keine Bearbeitung |