Question

Critical protein-protein interactions within the CARMA1-BCL10-MALT1 complex: Take-home points for the cell biologist

Answer 1

Protein-protein interactions within the CARMA1-BCL10-MALT1 complex:

• The T-cell receptor and B-cell receptor-dependent NF-B induction and lymphocyte activation are mediated by the CBM complex, which is made up of the proteins CARMA1, BCL10, and MALT1.
• Each of the proto-oncoproteins CARMA1, BCL10, and MALT1 is a somatic gain-of-function mutation or chromosomal translocation, and dysregulation of CBM signaling is a characteristic of numerous lymphoid malignancies, including Activated B-cell Diffuse Large B-cell Lymphoma.
• Moreover, a number of immunological dysregulation diseases have been linked to both gain- and loss-of-function germline mutations in CBM complex proteins.
• Over the past ten years, careful examination of the interactions of CBM components has yielded a wealth of detailed structural knowledge.
• Here, we discuss important discoveries about the molecular nature of these protein-protein interactions that have helped the research develop a detailed understanding of how these proteins come together to form high-order filamentous CBM complexes.
• Approaches to therapeutic suppression of the CBM complex have thus far centered on obstructing MALT1 protease activity in order to treat lymphoid malignancy and/or autoimmunity.
• The structural effects of MALT1 protease inhibitors on significant protein-protein interactions are also reviewed in detail.

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