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InflammAct Report Summary

Project ID: 616777
Funded under: FP7-IDEAS-ERC
Country: Germany

Periodic Report Summary 3 - INFLAMMACT (Activation and Regulation of the NLRP3 Inflammasome)

In the ERC consolidator grant InflammAct a group of scientists investigate the mechanisms by which the NLRP3 inflammasome is activated and regulated. Work in this group includes the application of chemical biology screens as a discovery tool to identify novel pathways involved in inflammasome activation downstream of chemically and physically diverse triggers of the NLRP3 inflammasome and mass spectroscopy based techniques to identify novel post translational modifications of NLRP3.
We have discovered that the NLRP3 inflammasome is regulated by a phosphorylation of the PYD domain at position serine 5. Phosphorylation at this residue prevents molecular interaction of the PYD domain of NLRP3 with the PYD domain of ASC. A dephosphorylation event at S5 is required for NLRP3 activation by various triggers. These data suggest that NLRP3 inflammasome activation can only proceed in cells in which a certain balance between kinase and phosphatase activity is present.

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