Probes to Monitor Activity of the Paracaspase MALT1

Hachmann, Janna; Edgington-Mitchell, Laura E.; Poręba, Marcin; Sanman, Laura E.; Drąg, Marcin; Bogyo, Matthew; Salvesen, Guy S.

doi:10.1016/j.chembiol.2014.11.011

Cited by 25 publications

(36 citation statements)

References 49 publications

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“…The need to distinguish between active and inactive MALT1 led to the development of activity-based probes (also known as active-site probes) directed against MALT1 [111, 112]. In addition to inhibiting MALT1, the main advantage of the probes is their ability to label and thereby visualize active MALT1 both in the recombinant in vitro setting and in the cellular context extending to endogenous MALT1.…”

Section: Relevance Of Individual Substrate Cleavage Eventsmentioning

confidence: 99%

“…Biotin as well as fluorophores are common [113, 114]. The activity-based probes developed by the Krappmann group as well as our laboratory utilized the specificity of MALT1 combined with an AOMK warhead, which is highly selective for Cys proteases, as well as different labels leading to the general format label-L(V/R)SR-AOMK [111, 112]. …”

Section: Relevance Of Individual Substrate Cleavage Eventsmentioning

confidence: 99%

“…An example includes elucidation of the question whether posttranslational modifications of MALT1 such as monoubiquitination [115, 116] are important for its activity. Additionally, applications in inhibitor screens could be envisioned.…”

Section: Relevance Of Individual Substrate Cleavage Eventsmentioning

confidence: 99%

See 2 more Smart Citations

The Paracaspase MALT1

Hachmann

Salvesen

2016

Biochimie

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The human paracaspase MALT1 is a caspase homolog that plays a central role in NF-κB signaling. Over the past few years it has become clear that this is due to a combination of its scaffolding and proteolytic function. Knockout mice and mice expressing a catalytically dead variant of the protease have provided valuable information. This review aims to provide an overview of recent developments regarding the enzymatic mechanism and specificity of MALT1, its substrates discovered to date, different mouse models, as well as the role of MALT1 in NF-κB signaling downstream of a variety of different receptors.

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Section: Relevance Of Individual Substrate Cleavage Eventsmentioning

confidence: 99%

Section: Relevance Of Individual Substrate Cleavage Eventsmentioning

confidence: 99%

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The Paracaspase MALT1

Hachmann

Salvesen

2016

Biochimie

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“…Frozen tissue blocks were sectioned, mounted on Superfrost/Plus slides (Fisher Scientific), fixed in ice-cold acetone, and blocked with PBS with 5% FBS, plus the inhibitor E-64 at 10 µM to block endogenous cysteine proteases for the detection of MALT1 activity. The sections were stained with the following reagents: αIgD, αCD45.1, αCD45.2, αKi67 (clone S01A15) (eBioscience), peanut agglutinin (Vector Labs), and the MALT1 activity probe Cy5-LVSR-AOMK (23). Imaging was acquired on a Zeiss Axio ImagerM1 microscope using the Slidebook software (Intelligent Imaging Innovations).…”

Section: Methodsmentioning

confidence: 99%

Differing Requirements for MALT1 Function in Peripheral B Cell Survival and Differentiation

Lee

Zhu

Hachmann

et al. 2017

The Journal of Immunology

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During a T cell-dependent immune response, formation of the germinal center (GC) is essential for the generation of high-affinity plasma cells and memory B cells. The canonical NF-κB pathway has been implicated in the initiation of GC reaction, and defects in this pathway have been linked to immune deficiencies. The paracaspase MALT1 plays an important role in regulating NF-κB activation upon triggering of antigen receptors. Although previous studies have reported that MALT1 deficiency abrogates the GC response, the relative contribution of B cells and T cells to the defective phenotype remains unclear. We utilized chimeric mouse models to demonstrate that MALT1 function is required in B cells for GC formation. This role is restricted to BCR signaling where MALT1 is critical for B cell proliferation and survival. Moreover, the pro-apoptotic signal transmitted in the absence of MALT1 is dominant to the pro-survival effects of T cell-derived stimuli. In addition to GC B cell differentiation, MALT1 is required for plasma cell differentiation, but not mitogenic responses. Lastly, we show that ectopic expression of Bcl-2 can partially rescue the GC phenotype in MALT1-deficient animals by prolonging the lifespan of BCR-activated B cells, but plasma cell differentiation and antibody production remain defective. Thus, our data uncover previously unappreciated aspects of MALT1 function in B cells and highlight its importance in humoral immunity.

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“…MALT1 can be auto-cleaved (Baens et al, 2014), but labeling with activity-based probes shows that MALT1 is active in its full length form Hachmann et al, 2015). Induction of catalytic activity involves conformational changes in the C-terminal Ig3 domain, which exerts an auto-inhibitory function but it is also essential for paracaspase activity (Wiesmann et al, 2012).…”

Section: Malt1 -A Scaffold and A Proteasementioning

confidence: 99%

Lymphocyte signaling and activation by the CARMA1-BCL10-MALT1 signalosome

Meininger

Krappmann

2016

Biological Chemistry

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Abstract:The CARMA1-BCL10-MALT1 (CBM) signalosome triggers canonical NF-κB signaling and lymphocyte activation upon antigen-receptor stimulation. Genetic studies in mice and the analysis of human immune pathologies unveiled a critical role of the CBM complex in adaptive immune responses. Great progress has been made in elucidating the fundamental mechanisms that dictate CBM assembly and disassembly. By bridging proximal antigenreceptor signaling to downstream signaling pathways, the CBM complex exerts a crucial scaffolding function. Moreover, the MALT1 subunit confers a unique proteolytic activity that is key for lymphocyte activation. Deregulated 'chronic' CBM signaling drives constitutive NF-κB signaling and MALT1 activation, which contribute to the development of autoimmune and inflammatory diseases as well as lymphomagenesis. Thus, the processes that govern CBM activation and function are promising targets for the treatment of immune disorders. Here, we summarize the current knowledge on the functions and mechanisms of CBM signaling in lymphocytes and how CBM deregulations contribute to aberrant signaling in malignant lymphomas.

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Probes to Monitor Activity of the Paracaspase MALT1

Cited by 25 publications

References 49 publications

The Paracaspase MALT1

The Paracaspase MALT1

Differing Requirements for MALT1 Function in Peripheral B Cell Survival and Differentiation

Lymphocyte signaling and activation by the CARMA1-BCL10-MALT1 signalosome

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