Article ; Online: Chlamydia trachomatis Prevents Apoptosis Via Activation of PDPK1-MYC and Enhanced Mitochondrial Binding of Hexokinase II.
2017 Volume 23, Page(s) 100–110
Abstract: ... approaches and imaging we demonstrate that Chlamydia-induced PDPK1-MYC signaling induces host hexokinase II ... either PDPK1 or MYC, which also disrupts intracellular development of Chlamydia trachomatis. These findings ... HKII), which becomes enriched and translocated to the mitochondria. Strikingly, preventing the HKII ...
| Abstract | The intracellular human bacterial pathogen Chlamydia trachomatis pursues effective strategies to protect infected cells against death-inducing stimuli. Here, we show that Chlamydia trachomatis infection evokes 3-phosphoinositide-dependent protein kinase-1 (PDPK1) signaling to ensure the completion of its developmental cycle, further leading to the phosphorylation and stabilization of MYC. Using biochemical approaches and imaging we demonstrate that Chlamydia-induced PDPK1-MYC signaling induces host hexokinase II (HKII), which becomes enriched and translocated to the mitochondria. Strikingly, preventing the HKII interaction with mitochondria using exogenous peptides triggers apoptosis of infected cells as does inhibiting either PDPK1 or MYC, which also disrupts intracellular development of Chlamydia trachomatis. These findings identify a previously unknown pathway activated by Chlamydia infection, which exhibits pro-carcinogenic features. Targeting the PDPK1-MYC-HKII-axis may provide a strategy to overcome therapeutic resistance of infection. |
|---|---|
| MeSH term(s) | 3-Phosphoinositide-Dependent Protein Kinases/metabolism ; Apoptosis ; Chlamydia Infections/metabolism ; Chlamydia Infections/microbiology ; Chlamydia trachomatis/physiology ; Enzyme Activation ; HeLa Cells ; Hexokinase/metabolism ; Host-Pathogen Interactions ; Humans ; Immunohistochemistry ; Mitochondria/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphorylation ; Proto-Oncogene Proteins c-myc/metabolism |
| Chemical Substances | Proto-Oncogene Proteins c-myc ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; Hexokinase (EC 2.7.1.1) ; 3-Phosphoinositide-Dependent Protein Kinases (EC 2.7.11.1) ; PDPK1 protein, human (EC 2.7.11.1) |
| Language | English |
| Publishing date | 2017-08-05 |
| Publishing country | Netherlands |
| Document type | Journal Article |
| ZDB-ID | 2851331-9 |
| ISSN | 2352-3964 |
| ISSN (online) | 2352-3964 |
| DOI | 10.1016/j.ebiom.2017.08.005 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
More links
Kategorien
In stock of ZB MED Cologne/Königswinter
| Zs.A 7090: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG) |
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.