Caspase recruitment domain-containing protein 11

Definition:

Adapter protein that plays a key role in adaptive immune response by transducing the activation of NF-kappa-B downstream of T-cell receptor (TCR) and B-cell receptor (BCR) engagement. Transduces signals downstream TCR or BCR activation via the formation of a multiprotein complex together with BCL10 and MALT1 that induces NF-kappa-B and MAP kinase p38 (MAPK11, MAPK12, MAPK13 and/or MAPK14) pathways. Upon activation in response to TCR or BCR triggering, CARD11 homooligomerizes to form a nucleating helical template that recruits BCL10 via CARD-CARD interaction, thereby promoting polymerization of BCL10 and subsequent recruitment of MALT1: this leads to I-kappa-B kinase (IKK) phosphorylation and degradation, and release of NF-kappa-B proteins for nuclear translocation. Its binding to DPP4 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner. Promotes linear ubiquitination of BCL10 by promoting the targeting of BCL10 to RNF31/HOIP. Stimulates the phosphorylation of BCL10. Also activates the TORC1 signaling pathway.

References:

[1]. Yong-Kang Yang, et al. Molecular Determinants of Scaffold-induced Linear Ubiquitinylation of B Cell Lymphoma/Leukemia 10 (Bcl10) during T Cell Receptor and Oncogenic Caspase Recruitment Domain-containing Protein 11 (CARD11) Signaling. J Biol Chem. 2016 Dec 9;291(50):25921-25936. [Content Brief]

[2]. Chi A Ma, et al. Germline hypomorphic CARD11 mutations in severe atopic disease. Nat Genet. 2017 Aug;49(8):1192-1201. [Content Brief]

[3]. Kei Ohnuma, et al. Caveolin-1 triggers T-cell activation via CD26 in association with CARMA1. J Biol Chem. 2007 Mar 30;282(13):10117-10131. [Content Brief]

[4]. Joel L Pomerantz, et al. CARD11 mediates factor-specific activation of NF-kappaB by the T cell receptor complex. EMBO J. 2002 Oct 1;21(19):5184-94. [Content Brief]

[5]. Qi Qiao, et al. Structural architecture of the CARMA1/Bcl10/MALT1 signalosome: nucleation-induced filamentous assembly. Mol Cell. 2013 Sep 26;51(6):766-79. [Content Brief]

[6]. O Gaide, et al. Carma1, a CARD-containing binding partner of Bcl10, induces Bcl10 phosphorylation and NF-kappaB activation. FEBS Lett. 2001 May 11;496(2-3):121-7. [Content Brief]

[7]. J Bertin, et al. CARD11 and CARD14 are novel caspase recruitment domain (CARD)/membrane-associated guanylate kinase (MAGUK) family members that interact with BCL10 and activate NF-kappa B. J Biol Chem. 2001 Apr 13;276(15):11877-82. [Content Brief]

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