A20 and ABIN-1 cooperate in balancing CBM complex-triggered NF-κB signaling in activated T cells

Yin, Hongli; Karayel, Özge; Chao, Ying-Yin; Seeholzer, Thomas; Hamp, Isabel; Plettenburg, Oliver; Gehring, Torben; Zielinski, Christina E.; Mann, Matthias; Krappmann, Daniel

doi:10.1007/s00018-022-04154-z

Cited by 18 publications

(14 citation statements)

References 59 publications

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“…A20 phosphorylation at serine 381 by an IκK leads to NF-κB pathway inhibition ( 11 ). In T and B cells, mucosa-associated lymphoid tissue transformation protein 1 (MALT1) mediates A20 cleavage following antigen receptor stimulation ( 29 ). The post-translational deubiquitylation modifications of A20 are related to K48- or K63-polyubiquitin chains ( 22 ).…”

Section: Regulation Of A20 and Its Relationship To Nf-κb Signaling In...mentioning

confidence: 99%

Current research into A20 mediation of allergic respiratory diseases and its potential usefulness as a therapeutic target

Liu

Yao

et al. 2023

Front. Immunol.

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Allergic airway diseases are characterized by excessive and prolonged type 2 immune responses to inhaled allergens. Nuclear factor κB (NF-κB) is a master regulator of the immune and inflammatory response, which has been implicated to play a prominent role in the pathogenesis of allergic airway diseases. The potent anti-inflammatory protein A20, termed tumor necrosis factor-α-inducible protein 3 (TNFAIP3), exerts its effects by inhibiting NF-κB signaling. The ubiquitin editing abilities of A20 have attracted much attention, resulting in its identification as a susceptibility gene in various autoimmune and inflammatory disorders. According to the results of genome-wide association studies, several TNFAIP3 gene locus nucleotide polymorphisms have been correlated to allergic airway diseases. In addition, A20 has been found to play a pivotal role in immune regulation in childhood asthma, particularly in the protection against environmentally mediated allergic diseases. The protective effects of A20 against allergy were observed in conditional A20-knockout mice in which A20 was depleted in the lung epithelial cells, dendritic cells, or mast cells. Furthermore, A20 administration significantly decreased inflammatory responses in mouse models of allergic airway diseases. Here, we review emerging findings elucidating the cellular and molecular mechanisms by which A20 regulates inflammatory signaling in allergic airway diseases, as well as discuss its potential as a therapeutic target.

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Section: Regulation Of A20 and Its Relationship To Nf-κb Signaling In...mentioning

confidence: 99%

Current research into A20 mediation of allergic respiratory diseases and its potential usefulness as a therapeutic target

Liu

Yao

et al. 2023

Front. Immunol.

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“…Some studies reported that A20 regulated the NF-κB signaling pathway and downregulated proinflammatory cytokines expression ( 25 – 27 ). A20 negatively regulates CARMA3- and BCL10-mediated NF-κB activation via its deubiquitylation activity ( 28 ).…”

Section: Regulation Of Carma3mentioning

confidence: 99%

CARMA3: A potential therapeutic target in non-cancer diseases

Gui

Zhang

et al. 2022

Front. Immunol.

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Caspase recruitment domain and membrane-associated guanylate kinase-like protein 3 (CARMA3) is a scaffold protein widely expressed in non-hematopoietic cells. It is encoded by the caspase recruitment domain protein 10 (CARD10) gene. CARMA3 can form a CARMA3-BCL10-MALT1 complex by recruiting B cell lymphoma 10 (BCL10) and mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1), thereby activating nuclear factor-κB (NF-κB), a key transcription factor that involves in various biological responses. CARMA3 mediates different receptors-dependent signaling pathways, including G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs). Inappropriate expression and activation of GPCRs and/or RTKs/CARMA3 signaling lead to the pathogenesis of human diseases. Emerging studies have reported that CARMA3 mediates the development of various types of cancers. Moreover, CARMA3 and its partners participate in human non-cancer diseases, including atherogenesis, abdominal aortic aneurysm, asthma, pulmonary fibrosis, liver fibrosis, insulin resistance, inflammatory bowel disease, and psoriasis. Here we provide a review on its structure, regulation, and molecular function, and further highlight recent findings in human non-cancerous diseases, which will provide a novel therapeutic target.

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“…Upon surface receptor activation, CARMA/CARD, BCL10 and MALT1 form the CBM complex serving as a protein assembly platform for NF-κB activation [ 17 , 21 ]. TRAF6 (TNF receptor associated factor 6) and NEMO are further recruited to the CBM complex to induce a NF-κB activation cascade in response to TCR, BCR and GPCR activation [ 21 , 22 , 23 ]. Mutations in genes belonging to the CBM complex and consequent loss of MALT1 function are associated with human combined immunodeficiency [ 14 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

Proteolytic Activity of the Paracaspase MALT1 Is Involved in Epithelial Restitution and Mucosal Healing

Wittner

Wagener

Wiese

et al. 2023

IJMS

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The paracaspase MALT1 is a crucial regulator of immune responses in various cellular contexts. Recently, there is increasing evidence suggesting that MALT1 might represent a novel key player in mucosal inflammation. However, the molecular mechanisms underlying this process and the targeted cell population remain unclear. In this study, we investigate the role of MALT1 proteolytic activity in the context of mucosal inflammation. We demonstrate a significant enrichment of MALT1 gene and protein expression in colonic epithelial cells of UC patients, as well as in the context of experimental colitis. Mechanistically we demonstrate that MALT1 protease function inhibits ferroptosis, a form of iron-dependent cell death, upstream of NF-κB signaling, which can promote inflammation and tissue damage in IBD. We further show that MALT1 activity contributes to STAT3 signaling, which is essential for the regeneration of the intestinal epithelium after injury. In summary, our data strongly suggests that the protease function of MALT1 plays a critical role in the regulation of immune and inflammatory responses, as well as mucosal healing. Understanding the mechanisms by which MALT1 protease function regulates these processes may offer novel therapeutic targets for the treatment of IBD and other inflammatory diseases.

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A20 and ABIN-1 cooperate in balancing CBM complex-triggered NF-κB signaling in activated T cells

Cited by 18 publications

References 59 publications

Current research into A20 mediation of allergic respiratory diseases and its potential usefulness as a therapeutic target

Current research into A20 mediation of allergic respiratory diseases and its potential usefulness as a therapeutic target

CARMA3: A potential therapeutic target in non-cancer diseases

Proteolytic Activity of the Paracaspase MALT1 Is Involved in Epithelial Restitution and Mucosal Healing

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