Regulation of IKK-epsilon and TRAF6 functions by posttranslational modifications

Antragsteller Professor Dr. M. Lienhard Schmitz
Fachliche Zuordnung Zellbiologie
Förderung Förderung von 2012 bis 2016
Projektkennung Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 219706149
 

Projektergebnisse

Erstellungsjahr 2017

Zusammenfassung der Projektergebnisse

The work from this project has revealed several important insights into the function of IKKɛ and TRAF6. We found an LPS-induced ubiquitination of IKKɛ at 5 residues in the C-terminus of the kinase. While inducible ubiquitination is mediated by TRAF6, the PARP10 ADP Ribosyltransferase removes the ubiquitin chains. Further experiments suggest a role of IKKɛ ubiquitination for the LPS-inducible expression of selected IKKɛ target genes. The LPS-inducible phosphorylation of TRAF6 at S279 occurred in 2 waves, as detected using a selfmade phospho-specific antibody. A phosphomimicking TRAF6 mutant showed a reduced ability for IKKɛ ubiquitination, consistent with the concept that this modification serves to restrict TRAF6 E3 ligase activity. This modification also increase TRAF6 stability, thus allowing to steer the amount and activity of this enzyme, thus leading to profound effects on LPS-stimulated gene expression. In addition, published data from this project identified and characterized the modification of TBK1 by SUMO, the contribution of IKKɛ for ERK signaling and the contribution of TRAF6 for mRNA metabolism.

Projektbezogene Publikationen (Auswahl)

DFG-Verfahren Sachbeihilfen
Beteiligte Personen Dr. Rita Moreno; Julian Rodriguez