| Description | CARD10 (NP_055365) is a 1032 amino-acid long protein with a molecular mass of 116 kDa. This protein consists of antiparallel alpha helices. CARD10 contains an N-terminal CARD domain, followed by a central coiled-coil (CC) domain and a C-terminal region encompassing a PDZ domain, a SH3 domain and a GUK domain (Wang et al., 2001). The CARD domain has a hydrophobic core and a hydrophilic outer surface, which mediate the interaction with the CARD domain of other proteins (Hayes-Bouchier et al., 2002; Sun, 2010). Coiled-coil domain is responsible for dimerization (Tanner et al., 2007). |
| |  |
| |
| | The structural domains of CARD10 protein are shown in different color boxes. CARD, caspase-recruitment domain; PDZ, PSD95, DLGA and ZO1 homology domain; SH3 domain, SRC-homology 3; and GUK domain, guanylate kinase. The numbers correspond to the amino-acid sequence. |
| |
| Expression | CARD10 is expressed in a variety of epithelial and mesenchymal tissues including heart, kidney and liver (Wang et al., 2001; McAllister-Lucas et al., 2007). It was reported that CARD10 is over-expressed in several cancers including breast, ovarian, colon, lung and glioma cancer. It was also shown that CARD10 deficiency affects cancer cell proliferation, survival, migration and invasion (Jiang et al., 2011). |
| Localisation | CARD10 is localized in the cytoplasm (Li et al., 2012). |
| Function | CARD10 participates in the organization of membrane signaling involved in cellular proliferation and death through highly specific CARD-CARD homophilic interactions. It appears that CARD10 acting as a scaffold is involved in NF-kB activation through interactions with Bcl10 and MALT1 (Grabiner et al., 2007; McAllister-Lucas et al., 2007). |
| Homology | CARD10 (CARMA3/Bimp1) shares a high degree of amino-acid sequence, structure and functional homology with CARD11 (CARMA1/Bimp2) and CARD14 (CARMA2/Bimp3). |
| Note | |
| | |
| Entity | Breast cancer |
| Disease | The levels of CARD10 protein are reported to be significantly higher in breast cancer than in normal breast tissue. It appears that CARD10 over-expression correlates with tumor, node and metastasis (TNM) stage, tumor size and ErbB2, also known as HER2 (from human epidermal growth factor receptor 2) or HER2/neu, over-expression. The observations that CARD10 leads to the up-regulation of cyclin D1, which is involved in proliferation, and of Bcl-2, a critical component in apoptosis, gene expressions in cell models derived from breast carcinoma (Zhao et al., 2013) is consistent with suggestion that CARD10 is involved in cell survival and proliferation. |
| | |
| | |
| Entity | Glioma |
| Disease | CARD10 is over-expressed in glioma and correlates with tumor grades (Grade I, II, III and IV) but not with age or gender. Knocking down of CARD10 expression is shown to inhibit the proliferation and invasion of glioma cell lines (Feng et al., 2014). |
| | |
| | |
| Entity | Colon cancer |
| Disease | CARD10 is also over-expressed in colon cancer samples compared to the normal tissue. The expression levels appear to associate with TNM and the proliferation index. Experimental studies suggest that CARD10 is a positive regulator of colon cancer proliferation (Miao et al., 2012). |
| | |
| | |
| Entity | Renal cell carcinoma |
| Disease | CARD10 mRNA expression was found to be significantly higher in renal cell carcinoma tissues compared with noncancerous renal tissues. Furthermore, it was shown that the high level of the CARD10 gene expression is associated with tumor size, histological differentiation, tumor stage and the presence of metastasis (Wu et al., 2013). |
| | |
| | |
| Entity | Ovarian cancer |
| Disease | CARD10 over-expression was observed to be positively correlated with tumor histology in ovarian cancer. It was shown that CARD10 depletion in various ovarian cancer cell lines inhibited cell proliferation and prevented cell cycle progression (Xie et al., 2014). It was also reported that protein kinase C alpha-CARD10 signaling axis plays an essential role in the lysophosphatidic acid (LPA)-induced in vitro invasion of ovarian cancer cells (Mahanivong et al., 2008). |
| | |
| | |
| Entity | Pancreatic carcinoma |
| Note | CARD10 was reported to be over-expressed in human pancreatic cancer (Du et al., 2014). Moreover, CARD10 appears to regulate malignant cell growth, invasion and NF-kB signaling (Du et al., 2014). |
| | |
| | |
| Entity | Non-small-cell lung cancer |
| Disease | As in other tissue cancers, the level of CARD10 protein is higher in non-small-cell lung cancer (NSCLC) than in normal lung tissues. There is a significant correlation between CARD10 levels and TNM stage (Li et al., 2012). |
| | |
| microRNA-146a inhibits G protein-coupled receptor-mediated activation of NF-kB by targeting CARD10 and COPS8 in gastric cancer. |
| Crone SG, Jacobsen A, Federspiel B, Bardram L, Krogh A, Lund AH, Friis-Hansen L. |
| Mol Cancer. 2012 Sep 20;11:71. doi: 10.1186/1476-4598-11-71. |
| PMID 22992343 |
| |
| CARMA3 is upregulated in human pancreatic carcinoma, and its depletion inhibits tumor proliferation, migration, and invasion. |
| Du S, Jia L, Zhang Y, Fang L, Zhang X, Fan Y. |
| Tumour Biol. 2014 Jun;35(6):5965-70. doi: 10.1007/s13277-014-1791-6. Epub 2014 Mar 16. |
| PMID 24633921 |
| |
| CARMA3 is overexpressed in human glioma and promotes cell invasion through MMP9 regulation in A172 cell line. |
| Feng X, Miao G, Han Y, Xu Y. |
| Tumour Biol. 2014 Jan;35(1):149-54. doi: 10.1007/s13277-013-1018-2. Epub 2013 Jul 27. |
| PMID 23893382 |
| |
| CARMA3 deficiency abrogates G protein-coupled receptor-induced NF-{kappa}B activation. |
| Grabiner BC, Blonska M, Lin PC, You Y, Wang D, Sun J, Darnay BG, Dong C, Lin X. |
| Genes Dev. 2007 Apr 15;21(8):984-96. |
| PMID 17438001 |
| |
| CARMA3 is crucial for EGFR-Induced activation of NF-kB and tumor progression. |
| Jiang T, Grabiner B, Zhu Y, Jiang C, Li H, You Y, Lang J, Hung MC, Lin X. |
| Cancer Res. 2011 Mar 15;71(6):2183-92. doi: 10.1158/0008-5472.CAN-10-3626. |
| PMID 21406399 |
| |
| Overexpression of CARMA3 in non-small-cell lung cancer is linked for tumor progression. |
| Li Z, Qu L, Dong Q, Huang B, Li H, Tang Z, Xu Y, Luo W, Liu L, Qiu X, Wang E. |
| PLoS One. 2012;7(5):e36903. doi: 10.1371/journal.pone.0036903. Epub 2012 May 15. |
| PMID 22615840 |
| |
| Protein kinase C alpha-CARMA3 signaling axis links Ras to NF-kappa B for lysophosphatidic acid-induced urokinase plasminogen activator expression in ovarian cancer cells. |
| Mahanivong C, Chen HM, Yee SW, Pan ZK, Dong Z, Huang S. |
| Oncogene. 2008 Feb 21;27(9):1273-80. Epub 2007 Aug 27. |
| PMID 17724468 |
| |
| CARMA3/Bcl10/MALT1-dependent NF-kappaB activation mediates angiotensin II-responsive inflammatory signaling in nonimmune cells. |
| McAllister-Lucas LM, Ruland J, Siu K, Jin X, Gu S, Kim DS, Kuffa P, Kohrt D, Mak TW, Nunez G, Lucas PC. |
| Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):139-44. Epub 2006 Nov 13. |
| PMID 17101977 |
| |
| CARMA3 is overexpressed in colon cancer and regulates NF-kB activity and cyclin D1 expression. |
| Miao Z, Zhao T, Wang Z, Xu Y, Song Y, Wu J, Xu H. |
| Biochem Biophys Res Commun. 2012 Sep 7;425(4):781-7. doi: 10.1016/j.bbrc.2012.07.152. Epub 2012 Aug 2. |
| PMID 22884800 |
| |
| GPCR-CARMA3- NF-kappaB signaling axis: A novel drug target for cancer therapy. |
| Sun JY. |
| Clinical Oncology and Cancer Research. 2010 June;7(3):159-168. |
| |
| CARMA1 coiled-coil domain is involved in the oligomerization and subcellular localization of CARMA1 and is required for T cell receptor-induced NF-kappaB activation. |
| Tanner MJ, Hanel W, Gaffen SL, Lin X. |
| J Biol Chem. 2007 Jun 8;282(23):17141-7. Epub 2007 Apr 11. |
| PMID 17428801 |
| |
| Card10 is a novel caspase recruitment domain/membrane-associated guanylate kinase family member that interacts with BCL10 and activates NF-kappa B. |
| Wang L, Guo Y, Huang WJ, Ke X, Poyet JL, Manji GA, Merriam S, Glucksmann MA, DiStefano PS, Alnemri ES, Bertin J. |
| J Biol Chem. 2001 Jun 15;276(24):21405-9. Epub 2001 Mar 20. |
| PMID 11259443 |
| |
| Evaluating the expression of CARMA3 as a prognostic tumor marker in renal cell carcinoma. |
| Wu GL, Yuan JL, Huang XD, Rong JF, Zhang LX, Liu YP, Wang FL. |
| Tumour Biol. 2013 Dec;34(6):3431-5. doi: 10.1007/s13277-013-0917-6. Epub 2013 Jun 15. |
| PMID 23771851 |
| |
| CARMA3 overexpression accelerates cell proliferation and inhibits paclitaxel-induced apoptosis through NF-kB regulation in breast cancer cells. |
| Zhao T, Miao Z, Wang Z, Xu Y, Wu J, Liu X, You Y, Li J. |
| Tumour Biol. 2013 Oct;34(5):3041-7. doi: 10.1007/s13277-013-0869-x. Epub 2013 May 25. |
| PMID 23708960 |
| |
