MALT1 Phosphorylation Controls Activation of T Lymphocytes and Survival of ABC-DLBCL Tumor Cells.

Abstract:

:The CARMA1/CARD11-BCL10-MALT1 (CBM) complex bridges T and B cell antigen receptor (TCR/BCR) ligation to MALT1 protease activation and canonical nuclear factor κB (NF-κB) signaling. Using unbiased mass spectrometry, we discover multiple serine phosphorylation sites in the MALT1 C terminus after T cell activation. Phospho-specific antibodies reveal that CBM-associated MALT1 is transiently hyper-phosphorylated upon TCR/CD28 co-stimulation. We identify a dual role for CK1α as a kinase that is essential for CBM signalosome assembly as well as MALT1 phosphorylation. Although MALT1 phosphorylation is largely dispensable for protease activity, it fosters canonical NF-κB signaling in Jurkat and murine CD4 T cells. Moreover, constitutive MALT1 phosphorylation promotes survival of activated B cell-type diffuse large B cell lymphoma (ABC-DLBCL) cells addicted to chronic BCR signaling. Thus, MALT1 phosphorylation triggers optimal NF-κB activation in lymphocytes and survival of lymphoma cells.

journal_name

Cell Rep

journal_title

Cell reports

authors

Gehring T,Erdmann T,Rahm M,Graß C,Flatley A,O'Neill TJ,Woods S,Meininger I,Karayel O,Kutzner K,Grau M,Shinohara H,Lammens K,Feederle R,Hauck SM,Lenz G,Krappmann D

doi

10.1016/j.celrep.2019.09.040

subject

Has Abstract

pub_date

2019-10-22 00:00:00

pages

873-888.e10

issue

4

issn

2211-1247

pii

S2211-1247(19)31228-8

journal_volume

29

pub_type

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