MALT1 Is an Essential Regulator of Antigen Receptor Mediated NF-kappaB Activation.
Bibliographic record
Abstract
Abstract The translocation t(11;18)(q21;q21) is the most common chromosomal abnormality in lymphomas of mucosa associated lymphoid tissue (MALT lymphoma). Molecular cloning of the breakpoint demonstrated that t(11;18) leads to the fusion of the IAP2 gene to the novel gene MALT1. MALT1 encodes a paracaspase that can bind to BCL10 but its cellular function was unknown. We have previously demonstrated that BCL10, which is involved in independent MALT lymphoma translocations, functions as a positive regulator of lymphocyte proliferation. BCL10 connects antigen receptor signaling in B and T cells to NF-kappa B activation. To identify the physiological role of MALT1 we have now disrupted the MALT1 gene in mice. Here we are using both MALT1 and BCL10 deficient animals and show that MALT1 is essential for functional T cell activation, proliferation and cytokine production in response to T cell receptor (TCR) ligation. Similar to BCL10 we found MALT1 to be strictly required for signal-specific NF-kappaB activation in response to TCR ligation but not for TNF-alpha or IL-1 signaling. MALT1 operates downstream of BCL10, controls the catalytic activity of IKK and additionally regulates signaling of p38 and JNK MAP kinases. Moreover we found MALT1 to be critical for B1 and marginal zone (MZ) B cell development. In contrast to BCL10 disruption however, inactivation of MALT1 has only mild effects on conventional B2 B cell activation, BCR induced NF-kappaB signaling in splenic B lymphocytes and does not cause defects during embryonic development. Thus, MALT1 is an essential regulator of BCL10 mediated NF-kB induction that is differentially required depending on the cellular context. Together these data support the view that normal expression of BCL10 and MALT1 are necessary for controlled NF-kB signaling in lymphocytes whereas deregulation of either BCL10 or MALT1 through chromosomal translocation results in increased lymphocyte growth and survival
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".