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Your search keyword '"Graß, Carina"' showing total 2 results
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2 results on '"Graß, Carina"'

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

Author

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, and Krappmann D

Subjects
Amino Acid Motifs, Animals, B-Cell CLL-Lymphoma 10 Protein metabolism, CARD Signaling Adaptor Proteins metabolism, CD28 Antigens metabolism, Casein Kinase Ialpha metabolism, Cells, Cultured, Guanylate Cyclase metabolism, HEK293 Cells, Humans, Jurkat Cells, Mice, Mice, Inbred C57BL, Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein chemistry, NF-kappa B metabolism, Phosphorylation, Lymphocyte Activation, Lymphoma, Large B-Cell, Diffuse immunology, Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein metabolism, Signal Transduction, T-Lymphocytes immunology
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., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Published
2019
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2. XIAP Loss Triggers RIPK3- and Caspase-8-Driven IL-1β Activation and Cell Death as a Consequence of TLR-MyD88-Induced cIAP1-TRAF2 Degradation.

Author

Lawlor KE, Feltham R, Yabal M, Conos SA, Chen KW, Ziehe S, Graß C, Zhan Y, Nguyen TA, Hall C, Vince AJ, Chatfield SM, D'Silva DB, Pang KC, Schroder K, Silke J, Vaux DL, Jost PJ, and Vince JE

Subjects
Animals, Caspase 8 genetics, Cell Death, Inhibitor of Apoptosis Proteins deficiency, Inhibitor of Apoptosis Proteins genetics, Interleukin-1beta genetics, Mice, Mice, Knockout, Myeloid Differentiation Factor 88 genetics, Proteolysis, Receptor-Interacting Protein Serine-Threonine Kinases genetics, TNF Receptor-Associated Factor 2 genetics, Toll-Like Receptors genetics, Caspase 8 metabolism, Inhibitor of Apoptosis Proteins metabolism, Interleukin-1beta metabolism, Myeloid Differentiation Factor 88 metabolism, Receptor-Interacting Protein Serine-Threonine Kinases metabolism, TNF Receptor-Associated Factor 2 metabolism, Toll-Like Receptors metabolism
Abstract

X-linked Inhibitor of Apoptosis (XIAP) deficiency predisposes people to pathogen-associated hyperinflammation. Upon XIAP loss, Toll-like receptor (TLR) ligation triggers RIPK3-caspase-8-mediated IL-1β activation and death in myeloid cells. How XIAP suppresses these events remains unclear. Here, we show that TLR-MyD88 causes the proteasomal degradation of the related IAP, cIAP1, and its adaptor, TRAF2, by inducing TNF and TNF Receptor 2 (TNFR2) signaling. Genetically, we define that myeloid-specific cIAP1 loss promotes TLR-induced RIPK3-caspase-8 and IL-1β activity in the absence of XIAP. Importantly, deletion of TNFR2 in XIAP-deficient cells limited TLR-MyD88-induced cIAP1-TRAF2 degradation, cell death, and IL-1β activation. In contrast to TLR-MyD88, TLR-TRIF-induced interferon (IFN)β inhibited cIAP1 loss and consequent cell death. These data reveal how, upon XIAP deficiency, a TLR-TNF-TNFR2 axis drives cIAP1-TRAF2 degradation to allow TLR or TNFR1 activation of RIPK3-caspase-8 and IL-1β. This mechanism may explain why XIAP-deficient patients can exhibit symptoms reminiscent of patients with activating inflammasome mutations., (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)

Published
2017
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