CARMA3: A novel scaffold protein in regulation of NF-κB activation and diseases

Sun, Jingbo

doi:10.4331/wjbc.v1.i12.353

Cited by 24 publications

(20 citation statements)

References 102 publications

(147 reference statements)

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“…This finding includes mutations in the CARD10 , PPP1R39 , SAFB2 , and STARD9 genes. CARD10 is associated with the activation of the NK-kB signaling pathway and is known to have clinical implications in gastric cancer, colon cancer, and non-small cell lung cancer [47]–[51]. A potential role for changes in the PPP1R39 gene has also been suggested in the development of human cancers [52].…”

Section: Discussionmentioning

confidence: 99%

Genetic Aberrations in Imatinib-Resistant Dermatofibrosarcoma Protuberans Revealed by Whole Genome Sequencing

et al. 2013

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Dermatofibrosarcoma protuberans (DFSP) is a very rare soft tissue sarcoma. DFSP often reveals a specific chromosome translocation, t(17;22)(q22;q13), which results in the fusion of collagen 1 alpha 1 (COL1A1) gene and platelet-derived growth factor-B (PDGFB) gene. The COL1A1-PDGFB fusion protein activates the PDGFB receptor and resultant constitutive activation of PDGFR receptor is essential in the pathogenesis of DFSP. Thus, blocking PDGFR receptor activation with imatinib has shown promising activity in the treatment of advanced and metastatic DFSP. Despite the success with targeted agents in cancers, acquired drug resistance eventually occurs. Here, we tried to identify potential drug resistance mechanisms against imatinib in a 46-year old female with DFSP who initially responded well to imatinib but suffered rapid disease progression. We performed whole-genome sequencing of both pre-treatment and post-treatment tumor tissue to identify the mutational events associated with imatinib resistance. No significant copy number alterations, insertion, and deletions were identified during imatinib treatment. Of note, we identified newly emerged 8 non-synonymous somatic mutations of the genes (ACAP2, CARD10, KIAA0556, PAAQR7, PPP1R39, SAFB2, STARD9, and ZFYVE9) in the imatinib-resistant tumor tissue. This study revealed diverse possible candidate mechanisms by which imatinib resistance to PDGFRB inhibition may arise in DFSP, and highlights the usefulness of whole-genome sequencing in identifying drug resistance mechanisms and in pursuing genome-directed, personalized anti-cancer therapy.

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Section: Discussionmentioning

confidence: 99%

Genetic Aberrations in Imatinib-Resistant Dermatofibrosarcoma Protuberans Revealed by Whole Genome Sequencing

et al. 2013

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“…This arrangement tethers the GUK domain to the SH3 bA-D fold through the bE/bF interface. Moreover, these structural features also seem to be conserved in the SH3-GUK modules in another CARD-MAGUK family, CARMA3, that regulates GPCR-and epidermal growth factor receptor-induced NF-kB activation in non-immune cells 2,3 (Supplementary Fig. 3).…”

Section: Resultsmentioning

confidence: 99%

“…B-cell lymphoma 10 (BCL10) and mucosa-associated lymphoid tissue lymphoma translocation gene 1 (MALT1) form a complex essential for NF-kB activation signalling through immunoreceptor tyrosine-based activation motif-coupled receptors, G-protein-coupled receptors and epidermal growth factor receptor [1][2][3] . CARMA1, also known as caspase recruitment domain 11 (CARD11), is a member of the CARD-containing membrane-associated guanylate kinase (MAGUK) family (CARD-MAGUKs) and contains an aminoterminal CARD, a coiled-coil (C-C) domain, and a MAGUK signature motif comprising a PDZ domain, a Src homology 3 (SH3) domain and a GUK domain in the COOH terminus.…”

mentioning

confidence: 99%

Clustering of CARMA1 through SH3–GUK domain interactions is required for its activation of NF-κB signalling

et al. 2015

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CARMA1-mediated NF-kB activation controls lymphocyte activation through antigen receptors and survival of some malignant lymphomas. CARMA1 clusters are formed on physiological receptor-mediated activation or by its oncogenic mutation in activated B-cell-diffuse large B-cell lymphomas (ABC-DLBCLs) with constitutive NF-kB activation. However, regulatory mechanisms and relevance of CARMA1 clusters in the NF-kB pathway are unclear. Here we show that SH3 and GUK domain interactions of CARMA1 link CARMA1 clustering to signal activation. SH3 and GUK domains of CARMA1 interact by either intra-or intermolecular mechanisms, which are required for activation-induced assembly of CARMA1. Disruption of these interactions abolishes the formation of CARMA1 microclusters at the immunological synapse, CARMA-regulated signal activation following antigen receptor stimulation as well as spontaneous CARMA1 clustering and NF-kB activation by the oncogenic CARMA1 mutation in ABC-DLBCLs. Thus, the SH3-GUK interactions that regulate CARMA1 cluster formations are promising therapeutic targets for ABC-DLBCLs.

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“…In immune cells, the CARD of BCL10 functions as an oligomerization region and interacts with the CARD of the CARD membraneassociated guanylate kinase (CARMA) 1 (6,7), which is required for activation of the NFB pathway (8 -12). In nonimmune cells, such as endothelial cells, a CARMA3 signalo-some containing BCL10 and mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1), operates to regulate the NFB signaling pathway (13,14). Disruption of the CARMA3 signalosome by genetic deletion of Bcl10 leads to dramatic reduction of vascular inflammation, illustrating that BCL10 is an essential component of the signaling complex (15).…”

mentioning

confidence: 99%

“…Induction of vascular permeability causes swelling, one of the four classic signs of inflammation, due to the action of proinflammatory agonists sensed by their cognate receptors expressed on microvascular endothelial cells (17). The CARMA3 signalosome amplifies signaling in response to proinflammatory agonists and mediates stimulus-dependent nuclear reprogramming (13)(14)(15)18), which depends on transcription factors NFB and AP-1 (13,16,18,19). Thus, the CARMA3 signalosome plays a pivotal role in shifting microvascular endothelial cells from a resting to activated state, integrating signaling pathways evoked by recognition of diverse agonists.…”

mentioning

confidence: 99%

The Adaptor CRADD/RAIDD Controls Activation of Endothelial Cells by Proinflammatory Stimuli

Qiao

Liu

Veach

et al. 2014

Journal of Biological Chemistry

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Background:The role of CRADD in endothelial cells is unknown. Results: CRADD attenuates responses to proinflammatory agonists in endothelial cells and stabilizes their barrier function. Conclusion: CRADD plays a pivotal role in maintaining the integrity of the endothelial barrier. Significance: Understanding the role of CRADD as a physiologic rheostat of perturbed endothelial cells informs development of CRADD-based measures to stabilize endothelial integrity.

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CARMA3: A novel scaffold protein in regulation of NF-κB activation and diseases

Cited by 24 publications

References 102 publications

Genetic Aberrations in Imatinib-Resistant Dermatofibrosarcoma Protuberans Revealed by Whole Genome Sequencing

Genetic Aberrations in Imatinib-Resistant Dermatofibrosarcoma Protuberans Revealed by Whole Genome Sequencing

Clustering of CARMA1 through SH3–GUK domain interactions is required for its activation of NF-κB signalling

The Adaptor CRADD/RAIDD Controls Activation of Endothelial Cells by Proinflammatory Stimuli

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