Differential requirement for Malt1 in T and B cell antigen receptor signaling.
The translocation t(11;18)(q21;q21) involving MALT1 is the most common chromosomal abnormality in lymphomas of mucosa-associated lymphoid tissue. Although the paracaspase MALT1 can bind to BCL10, the physiological function of MALT1 is unknown. Using mouse models, we show that Malt1 is essential for T cell activation, proliferation, and IL-2 production in response to TCR ligation and strictly required for signal-specific NF-kappaB activation induced by the TCR but not TNF-alpha or IL-1 signaling. Malt1 operates downstream of Bcl10, controls the catalytic activity of the canonical IKK complex, and regulates the signaling of Jnk and p38 MAP kinases. In contrast to Bcl10 disruption, however, inactivation of Malt1 has only mild effects on B cell activation and does not cause defects during neurodevelopment. Thus, Malt1 is an essential regulator of Bcl10 signaling that is differentially required depending on cellular context.
Ruland
Jürgen
J
Advanced Medical Discovery Institute, Ontario Cancer Institute, University of Toronto, 620 University Avenue, Toronto, Ontario M5G 2C1, Canada. jruland@lrz.tu-muenchen.de
Duncan
Gordon S
GS
Wakeham
Andrew
A
Mak
Tak W
TW
D000818:Animals; D020169:Caspases; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; D016328:NF-kappa B / Q000378:metabolism; D009363:Neoplasm Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology / Q000502:physiology*
D016328:NF-kappa B; D009363:Neoplasm Proteins; D011947:Receptors, Antigen, B-Cell; D011948:Receptors, Antigen, T-Cell; D020169:Caspases; C498509:Malt1 protein, mouse; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein