Critical protein-protein interactions within the CARMA1-BCL10-MALT1 complex: Take-home points for the cell biologist.
Cell Immunol
; 355: 104158, 2020 09.
Article
em En
| MEDLINE
| ID: mdl-32721634
ABSTRACT
The CBM complex, which is composed of the proteins CARMA1, BCL10, and MALT1, serves multiple pivotal roles as a mediator of T-cell receptor and B-cell receptor-dependent NF-κB induction and lymphocyte activation. CARMA1, BCL10, and MALT1 are each proto-oncoproteins and dysregulation of CBM signaling, as a result of somatic gain-of-function mutation or chromosomal translocation, is a hallmark of multiple lymphoid malignancies including Activated B-cell Diffuse Large B-cell Lymphoma. Moreover, loss-of-function as well as gain-of-function germline mutations in CBM complex proteins have been associated with a range of immune dysregulation syndromes. A wealth of detailed structural information has become available over the past decade through meticulous interrogation of the interactions between CBM components. Here, we review key findings regarding the biochemical nature of these protein-protein interactions which have ultimately led the field to a sophisticated understanding of how these proteins assemble into high-order filamentous CBM complexes. To date, approaches to therapeutic inhibition of the CBM complex for the treatment of lymphoid malignancy and/or auto-immunity have focused on blocking MALT1 protease function. We also review key studies relating to the structural impact of MALT1 protease inhibitors on key protein-protein interactions.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Adaptadoras de Sinalização CARD
/
Proteína de Translocação 1 do Linfoma de Tecido Linfoide Associado à Mucosa
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Proteína 10 de Linfoma CCL de Células B
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Guanilato Ciclase
Limite:
Humans
Idioma:
En
Revista:
Cell Immunol
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos