COP9 signalosome controls the Carma1-Bcl10-Malt1 complex upon T-cell stimulation

Verena Welteke; Andrea Eitelhuber; Michael Düwel; Katrin Schweitzer; Michael Naumann; Daniel Krappmann

doi:10.1038/embor.2009.64

COP9 signalosome controls the Carma1-Bcl10-Malt1 complex upon T-cell stimulation

EMBO Rep. 2009 Jun;10(6):642-8. doi: 10.1038/embor.2009.64. Epub 2009 May 15.

Authors

Verena Welteke¹, Andrea Eitelhuber, Michael Düwel, Katrin Schweitzer, Michael Naumann, Daniel Krappmann

Affiliation

¹ Department Cellular Signal Integration, Helmholtz Zentrum München-German Research Center for Environmental Health, Institute of Toxicology, Ingolstädter Landstrasse 1, Neuherberg 85764, Germany.

Abstract

The Carma1-Bcl10-Malt1 (CBM) complex connects T-cell receptor (TCR) signalling to the canonical IkappaB kinase (IKK)/NF (nuclear factor)-kappaB pathway. Earlier studies have indicated that the COP9 signalosome (CSN), a pleiotropic regulator of the ubiquitin/26S proteasome system, controls antigen responses in T cells. The CSN is required for the degradation of the NF-kappaB inhibitor IkappaBalpha, but other molecular targets involved in T-cell signalling remained elusive. Here, we identify the CSN subunit 5 (CSN5) as a new interactor of Malt1 and Carma1. T-cell activation triggers the recruitment of the CSN to the CBM complex, and CSN downregulation impairs TCR-induced IKK activation. Furthermore, the CSN is required for maintaining the stability of Bcl10 in response to T-cell activation. Taken together, our data provide evidence for a functional link between the evolutionarily conserved CSN and the adaptive immunoregulatory CBM complex in T cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing / metabolism*
B-Cell CLL-Lymphoma 10 Protein
CARD Signaling Adaptor Proteins / metabolism*
COP9 Signalosome Complex
Caspases / metabolism*
Enzyme Activation
Guanylate Cyclase / metabolism*
Humans
I-kappa B Kinase / metabolism
Jurkat Cells
Lymphocyte Activation / immunology*
Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein
Multiprotein Complexes / metabolism*
Neoplasm Proteins / metabolism*
Peptide Hydrolases / metabolism*
Protein Binding
Protein Stability
Protein Subunits
Receptors, Antigen, T-Cell / metabolism
T-Lymphocytes / cytology
T-Lymphocytes / enzymology
T-Lymphocytes / immunology*
Ubiquitination

Substances

Adaptor Proteins, Signal Transducing
B-Cell CLL-Lymphoma 10 Protein
BCL10 protein, human
CARD Signaling Adaptor Proteins
Multiprotein Complexes
Neoplasm Proteins
Protein Subunits
Receptors, Antigen, T-Cell
I-kappa B Kinase
Peptide Hydrolases
COP9 Signalosome Complex
Caspases
MALT1 protein, human
Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein
CARD11 protein, human
Guanylate Cyclase