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

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

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

Abstract

The Carma1–Bcl10–Malt1 (CBM) complex connects T‐cell receptor (TCR) signalling to the canonical IκB kinase (IKK)/NF (nuclear factor)‐κB 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‐κB inhibitor IκBα, 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.

Keywords

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

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    selected citations
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    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    31
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
31
Top 10%
Top 10%
Top 10%
gold