Targeting MALT1 Proteolytic Activity in Immunity, Inflammation and Disease: Good or Bad?

Annelies Demeyer; Jens Staal; Rudi Beyaert

doi:10.1016/j.molmed.2015.12.004

Targeting MALT1 Proteolytic Activity in Immunity, Inflammation and Disease: Good or Bad?

Trends Mol Med. 2016 Feb;22(2):135-150. doi: 10.1016/j.molmed.2015.12.004. Epub 2016 Jan 17.

Authors

Annelies Demeyer¹, Jens Staal¹, Rudi Beyaert²

Affiliations

¹ Inflammation Research Center, Unit of Molecular Signal Transduction in Inflammation, Vlaams Instituut voor Biotechnologie (VIB), 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9052 Ghent, Belgium.
² Inflammation Research Center, Unit of Molecular Signal Transduction in Inflammation, Vlaams Instituut voor Biotechnologie (VIB), 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9052 Ghent, Belgium. Electronic address: rudi.beyaert@irc.vib-ugent.be.

PMID: 26787500
DOI: 10.1016/j.molmed.2015.12.004

Abstract

MALT1 is a signaling protein that plays a key role in immunity, inflammation, and lymphoid malignancies. For a long time MALT1 was believed to function as a scaffold protein, providing an assembly platform for other signaling proteins. This view changed dramatically when MALT1 was also found to have proteolytic activity and a capacity to fine-tune immune responses. Preclinical studies have fostered the belief that MALT1 is a promising therapeutic target in autoimmunity and B cell lymphomas. However, recent studies have shown that mice expressing catalytically-inactive MALT1 develop multi-organ inflammation and autoimmunity, and thus have tempered this initial enthusiasm. We discuss recent findings, highlighting the urgent need for a better mechanistic and functional understanding of MALT1 in host defense and disease.

Keywords: MALT1; inflammation; lymphocytes; lymphoma; protease; therapeutic targeting.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Autoimmune Diseases / drug therapy*
Autoimmune Diseases / genetics
Autoimmune Diseases / pathology
Caspase Inhibitors / pharmacology*
Caspases / deficiency
Caspases / genetics*
Caspases / immunology
Gene Expression Regulation
Humans
Immunity, Innate / drug effects
Inflammation
Lymphocyte Activation
Lymphoma, B-Cell / drug therapy*
Lymphoma, B-Cell / genetics
Lymphoma, B-Cell / immunology
Lymphoma, B-Cell / pathology
Mice
Mice, Knockout
Molecular Targeted Therapy
Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein
NF-kappa B / genetics
NF-kappa B / immunology
Neoplasm Proteins / antagonists & inhibitors
Neoplasm Proteins / deficiency
Neoplasm Proteins / genetics*
Neoplasm Proteins / immunology
Proteolysis / drug effects
Signal Transduction

Substances

Caspase Inhibitors
NF-kappa B
Neoplasm Proteins
Caspases
MALT1 protein, human
Malt1 protein, mouse
Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein