| First Author | Hara H | Year | 2015 |
| Journal | Nat Commun | Volume | 6 |
| Pages | 5555 | PubMed ID | 25602919 |
| Mgi Jnum | J:219718 | Mgi Id | MGI:5629615 |
| Doi | 10.1038/ncomms6555 | Citation | Hara H, et al. (2015) Clustering of CARMA1 through SH3-GUK domain interactions is required for its activation of NF-kappaB signalling. Nat Commun 6:5555 |
| abstractText | CARMA1-mediated NF-kappaB 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-kappaB activation. However, regulatory mechanisms and relevance of CARMA1 clusters in the NF-kappaB 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-kappaB 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. |
