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MALT 1 – a universal soldier: multiple strategies to ensure NF ‐κB activation and target gene expression
Author(s) -
Afonina Inna S.,
Elton Lynn,
Carpentier Isabelle,
Beyaert Rudi
Publication year - 2015
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.13325
Subject(s) - microbiology and biotechnology , signal transduction , biology , t cell , acquired immune system , nf κb , proinflammatory cytokine , innate immune system , cancer research , immune system , immunology , inflammation
The paracaspase MALT 1 (mucosa associated lymphoid tissue lymphoma translocation gene 1) is an intracellular signaling protein that plays a key role in innate and adaptive immunity. It is essential for nuclear factor κB ( NF ‐κB) activation and proinflammatory gene expression downstream of several cell surface receptors. MALT 1 has been most studied in the context of T‐cell receptor‐induced NF ‐κB signaling, supporting T‐cell activation and proliferation. In addition, MALT 1 hyperactivation is associated with specific subtypes of B‐cell lymphoma, where it controls tumor cell proliferation and survival. For a long time, MALT 1 was believed to function solely as a scaffold protein, providing a platform for the assembly of other NF ‐κB signaling proteins. However, this view changed dramatically when MALT 1 was found to have proteolytic activity that further fine‐tunes signaling. MALT 1 proteolytic activity is essential for T‐cell activation and lymphomagenesis, suggesting that MALT 1 is a promising therapeutic target for the treatment of autoimmune diseases and distinct lymphoma entities. However, interference with MALT 1 activity may pose a dangerous threat to the normal functioning of the immune system and should be evaluated with great care. Here we discuss the current knowledge on the scaffold and protease functions of MALT 1, including an overview of its substrates and the functional implications of their cleavage.