IndraLab

"Indeed, CK1α deficiency abolished NF-κB signaling and MALT1 protease activation, as evident from loss of IκBα phosphorylation/degradation, NF-κB DNA binding, and MALT1-catalyzed CYLD or HOIL-1 cleavag[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

"At the same time, MALT1 could function as a protease activity upon TCR and CD28 co-stimulation to inactivate negative regulators of NF-kappaB signaling such as the A20 (also known as TNFAIP3), CYLD (cylindromatosis), RNase Regnase-1 as well as RelB and HOIL1 [XREF_BIBR - XREF_BIBR]."

"The requirement for MALT1 mediated CYLD cleavage for intact JNK signaling downstream of the TCR has been previously described XREF_BIBR."

"To assess whether BCR signaling results in MALT1-mediated CYLD cleavage, we treated cell lines with phorbol myristate acetate (PMA) and ionomycin, which activate protein kinase C (PKC), a key intermediate of BCR-controlled MALT1 activation."

"As expected, the targeting of MALT1 enzyme with the phenothiazine derivative mepazine, or the silencing of its expression with small interference RNA (siRNA) significantly reduced HOIL1 and CYLD proce[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

"Altogether, our findings establish an important role for MALT1-mediated CYLD cleavage in BCR signaling, canonical NF-κB activity, and consequently cell growth of BCR-dependent lymphomas, thereby providing novel insights into targeting MALT1 protease activity and ubiquitination enzymes as a promising therapeutic approach for these aggressive lymphomas."

"To assess whether MALT1-mediated CYLD cleavage directly contributes to growth of BCR-dependent lymphoma cell lines, we generated a CYLD mutant that can no longer be cleaved by MALT1 (CYLD R324 A) [31]."

"In addition, MALT1 promotes lymphocyte activation by cleaving A20 and CYLD, deubiquitinating enzymes that have inhibitory roles in the NF-kappaB and JNK pathway, respectively XREF_BIBR, XREF_BIBR, and by cleavage of BCL10, which promotes lymphocyte adhesion XREF_BIBR."

"MALT1-mediated cleavage of CYLD associates with CCR7-mediated migration of primary SMZL cells in vitro."

"Taken together, our data revealed that (1) CYLD is cleaved by MALT1, (2) these MALT1-mediated cleavage products of CYLD undergo rapid proteasomal degradation (inactivation), and (3) CYLD represses NF-κB activity and cell growth; hence, MALT-mediated cleavage of CYLD promotes NF-κB activity and growth of aggressive B-cell receptor-dependent lymphomas."

"To further confirm that MALT1 protease mediated the cleavage of MCPIP1 in macrophages, we used siRNA to knockdown MALT1 expression in macrophages, confirming that MALT1 promoted MCPIP1, but not A20, CYLD, BCL10 or RelB, degradation."

"Despite poorer transfection efficiency, TRAF6 was able to stimulate MALT1 paracaspase-induced CYLD cleavage in Jurkat JPM50.6 cells, which is consistent with the data obtained in the CRISPR-generated [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

"JNK activation has been connected to MALT1 catalysed CYLD cleavage XREF_BIBR."

"In endothelial cells, the activation of the GPCR PAR1 disrupts microtubules stability via MALT1-mediated CYLD processing and may therefore assist GEF-H1 activation [4] ."

"Taken together, our findings identify an important role for MALT1-mediated CYLD cleavage in BCR signaling, NF-kappaB activation and cell proliferation, which provides novel insights into the underlying molecular mechanisms and clinical potential of inhibitors of MALT1 and ubiquitination enzymes as promising therapeutics for DLBCL, MCL and potentially other B-cell malignancies."

"We found that a 12-h treatment with 1 µM MALT1i#2 is sufficient to block MALT1-mediated cleavage of CYLD and N4BP1 (Fig. 8 E)."

"Interestingly, treatment with a broad spectrum inhibitor of protein kinase C (PKC) enzymes, which are known upstream activators of CARD14 family proteins [43], not only failed to inhibit NF-κB/JNK/Akt phosphorylation, but also MALT1-mediated CYLD and A20 cleavage (Figure 5A), suggesting that constitutive CBM activation in PCa cells is mediated by a PKC-independent mechanism.While the scaffold function of MALT1 is required for NF-κB activation and gene expression, MALT1 proteolytic activity mainly controls gene expression at the posttranscriptional level by regulating mRNA stability of specific genes, including IL-6, in an NF-κB-independent manner (Figure 4A) [40]."