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Paper of the Month

p38 MAPK/MK2-dependent phosphorylation controls cytotoxic RIPK1 signaling in inflammation and infection

Manoj B. Menon1*,  Julia Gropengießer2*, Jessica Fischer1, Lena Novikova2, Anne Deuretzbacher2, Juri Lafera1, Hanna Schimmeck2, Nicole Czymmeck2, Natalia Ronkina1, Alexey Kotlyarov1, Martin Aepfelbacher2, Matthias Gaestel1, and Klaus Ruckdeschel2

Vollständiger Artikel: https://www.nature.com/articles/ncb3614externer Link

* These authors contributed equally to this work.
1 Institute of Cell Biochemistry, Hannover Medical School, Hannover, Germany
2 Institute for Medical Microbiology, Virology and Hygiene, University Medical Center Eppendorf, Hamburg, Germany

Bild: Erstautorin Julia Gropengießer

Erstautorin

 

Bacterial pathogens have developed sophisticated mechanisms to modulate host immune responses in order to establish infection. By exploring the mechanisms of Yersinia enterocolitica-induced cell death we disclosed a so far unknown feedback signaling circuit that determines the fate of eukaryotic cells. We identified p38MAPK/MK2-dependent phosphorylation of RIPK1 as central signaling checkpoint at the crossroads of infection, inflammation and cell death and deciphered the molecular mechanisms and consequences thereof in collaboration with colleagues of the Institute of Cell Biochemistry at the Medical School Hannover. Our work implies the crosstalk between MK2 and RIPK1 as master control loop of cell vitality in multiple stress conditions, thus impacting a broad spectrum of physiological and pathophysiological biological processes, including infection, development, organ injury and cancer. This gives an outstanding example on how the investigation of the virulence traits of pathogenic bacteria provides fundamental new insights into the regulation of host cell function and physiology.

Nature Cell

Kontakt:
Prof. Dr. Klaus Ruckdeschel
Institut für Medizinische Mikrobiologie, Virologie und Hygiene
Universitätsklinikum Eppendorf
Martinistr. 52
20246 Hamburg
Tel. 040-7410-58184
Email: k.ruckdeschel@uke.de