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GSK3β modulates NF-κB activation and RelB degradation through site-specific phosphorylation of BCL10.


ABSTRACT: Glycogen synthase kinase 3β (GSK3β) is a ubiquitously expressed serine/threonine kinase involved in the regulation of various cellular functions, such as energy homoeostasis, cell growth and developmental processes. More recently, GSK3β has been identified as a part of a protein complex involved in the regulation of the CARMA1-BCL10-MALT1 complex (CBM complex) formation, which is a key signalling event upon antigen receptor engagement of B and T cells, required for the activation of the NF-κB and JNK pathways. However, conflicting reports have been published regarding the role of GSK3β for the activation of the NF-κB signalling pathways. Therefore, we aimed to determine the impact of GSK3β on the NF-κB signalling induced upon T cell activation. Blocking GSK3β by either pharmacologic inhibitors (SB216763 and SB415286) or by RNAi caused a reduced proteolysis of the MALT1 targets CYLD1, BCL10 and RelB as well as diminished IκBα degradation, NF-κB DNA binding and NF-κB activity. This negative effect on NF-κB appears to be due to a diminished CBM complex formation caused by a reduced BCL10 phosphorylation. Taken together, we provide here evidence for a novel regulatory mechanism by which GSK3β affects NF-κB signalling in activated T cells.

SUBMITTER: Abd-Ellah A 

PROVIDER: S-EPMC5777991 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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GSK3β modulates NF-κB activation and RelB degradation through site-specific phosphorylation of BCL10.

Abd-Ellah Ali A   Voogdt Cornelia C   Krappmann Daniel D   Möller Peter P   Marienfeld Ralf B RB  

Scientific reports 20180122 1


Glycogen synthase kinase 3β (GSK3β) is a ubiquitously expressed serine/threonine kinase involved in the regulation of various cellular functions, such as energy homoeostasis, cell growth and developmental processes. More recently, GSK3β has been identified as a part of a protein complex involved in the regulation of the CARMA1-BCL10-MALT1 complex (CBM complex) formation, which is a key signalling event upon antigen receptor engagement of B and T cells, required for the activation of the NF-κB an  ...[more]

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