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CARD8 (caspase recruitment domain family, member 8)

Written2007-05Frank A. Kruyt
Department of Medical Oncology, VU University Medical Center, 1081 HV Amsterdam, The Netherlands kruyt@vumc.nl

(Note : for Links provided by Atlas : click)

Identity

Other aliasCARDINAL
DACAR
DKFZp779L0366
KIAA0955
MGC57162
NDPP1
TUCAN
LocusID (NCBI) 22900
Atlas_Id 913
Location 19q13.33  [Link to chromosome band 19q13]
Location_base_pair Starts at and ends at bp from pter
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
CARD8 (19q13.33) / BCKDHA (19q13.2)CARD8 (19q13.33) / CARD8 (19q13.33)CARD8 (19q13.33) / DDX19B (16q22.1)
CARD8 (19q13.33) / EXD3 (9q34.3)CARD8 (19q13.33) / RPA1 (17p13.3)CARD8 (19q13.33) / SULT2B1 (19q13.33)

DNA/RNA

Description The CARD8 gene contains 13 exons spanning over approximately 30 kb of genomic DNA
Transcription At least 5 transcripts have been identified generated by alternative splicing that together with different start codon usage yield different CARD8 isoforms. Gene products encoded by exons 1 to 13 and 5 to 13 yield TUCAN/CARD8-54-kDa and TUCAN/CARD8-48-kDa, respectively.

Protein

 
  Schematic representation of two CARD8 variants. The CARD domain, the NAC/DEFCAP/CARD7 homology domain, and the amino-terminal residues that differ between the isoforms are indicated.
Description The CARD8 gene encodes different CARD8 isoforms that contain the caspase-associated recruitment domain (CARD) in their carboxy-termini that acts as a protein-protein interaction interface. A 431 amino acids CARD8 protein of 48-kDa (TUCAN-48) has been best studied and more recently a 54-kDa isoform (TUCAN-54, 487 amino acids) was identified sharing the same CARD motif but with a different stretch of 80 amino-terminal residues. In the amino terminal part of the protein a NAC/DEFCAP/CARD7 homology domain is present.
Expression Normal tissue: wide and differential expression at mRNA level in tissues; present in heart, brain, lung, muscle, spleen, ovary; high in kidney, testis and spinal cord; absent in liver.
Cancer: the CARD8 (48 kDa) protein is differentially expressed in cancer. High levels of CARD8 expression were found in tumor cell lines, including breast, prostate, ovarian and colon cancer cells as well as high expression in non-small cell lung cancer (NSCLC) cells and with hardly detectable expression in normal lung, in contrast to a lack of expression in small-cell lung cancer cell lines. In tumor specimens from patients CARD8 expression has been demonstrated in colon cancer and non-small cell lung cancer. The 54-kDa CARD8 isoform has a different expression profile when compared to TUCAN/CARD8-48. For example a number of breast cancer cell lines do not express TUCAN/CARD8-54, although some of them express TUCAN/CARD8-48. Expression also varies widely among different tumor cell lines with high levels in colon cancer cells.
Localisation In MCF-7 cells overexpressed CARD8 localized to both the cytoplasmic and nuclear compartment. In specimens derived from colon cancer cells a predominant cytoplasmic expression was found, whereas in NSCLC tumor samples CARD8 was either exclusively nuclear or cytoplasmic or present in both compartments.
Function CARD8 belongs to the CARD family of proteins that play a role in apoptosis regulation and NF-kB signaling associated with the innate or adaptive immune response. For example the binding of CARDs present in caspase-9 and Apaf-1 mediate the assembly of the apoptosome in which caspase-9 is activated. CARD motifs have different binding selectivity towards each other and the presence of additional structural/ functional domains in the various CARD-containing proteins may also determine the choice of interaction partner.
In literature there is some controversy on the function of CARD8. Some reports mention an apoptosis inhibitory function of CARD8 involving its CARD-dependent binding to procaspase-9, whereas others did not find an association between CARD8 and caspase-9 and instead found either pro-apoptotic activity of CARD8 and associations with the inflammatory caspase-1 or the regulatory subunit of IkB kinase (NEMO) thereby suppressing NF-kB activation. Also an interaction between the p53-responsive gene DRAL (FLH2) and CARD8 has been reported resulting in the suppression of NF-kB activation. Furthermore, TUCAN/CARD8-54 was found to inhibit chemotherapy-induced caspase-9 activation and Fas ligand-induced caspase-8 activation. Based mainly on its proposed anti-apoptotic activity CARD8 is considered as a possible therapeutic target for cancer.
Homology CARD family proteins.

Mutations

Somatic Ten single nucleotide polymorphisms (SNPs) across TUCAN/CARD8 have been identified in healthy persons and patients suffering from inflammatory bowl disease.

Implicated in

Note
  
Entity Colon cancer
Prognosis TUCAN/CARD8 expression has been analyzed by immunohistochemistry in paraffin-embedded colon cancer specimens (N=102) derived from patients with clinical stage II that were surgically treated. TUCAN/CARD8 staining was stronger in colon cancer cells when compared to normal cells in 64% of the 102 specimens examined. Scoring staining intensity revealed a significant correlation between high TUCAN/CARD8 expression in tumor cells and shorter patient survival.
  
  
Entity Non-small cell lung cancer (NSCLC)
Prognosis The expression of TUCAN/CARD8 has been determined by immunohistochemistry in tumor specimens derived from NSCLC patients (N=49, stage III and IV) that received neoadjuvant or palliative chemotherapy. TUCAN/CARD8 expression was detected in 69% of the samples, showing exclusively cytoplasmic (27%) or nuclear (11%) staining, or in both compartments (31%). No correlation between response to chemotherapy or expression/ localization was found, although, cytoplasm-only staining NSCLC samples predicted shorter survival, suggesting a possible prognostic value.
  
  
Entity Inflammatory bowel disease (IBD)
Disease Crohn' disease and ulcerative colitis
Prognosis Patients with IBD (Crohn's disease (CD) and ulcerative colitis) and healthy individuals were genotyped for SNP. A significant association between a TUCAN SNP and CD was found. However, in other reports this association was not confirmed, rejecting TUCAN/CARD8 as a possible susceptibility gene for IBD.
  

Bibliography

CARD games in apoptosis and immunity.
Bouchier-Hayes L, Martin SJ
EMBO reports. 2002 ; 3 (7) : 616-621.
PMID 12101092
 
The expression of TUCAN, an inhibitor of apoptosis protein, in patients with advanced non-small cell lung cancer treated with chemotherapy.
Checinska A, Oudejans JJ, Span SW, Rodriguez JA, Kruyt FA, Giaccone G
Anticancer research. 2006 ; 26 (5B) : 3819-3824.
PMID 17094407
 
CARD proteins as therapeutic targets in cancer.
Damiano JS, Reed JC
Current drug targets. 2004 ; 5 (4) : 367-374.
PMID 15134219
 
Combined evidence from three large British Association studies rejects TUCAN/CARD8 as an IBD susceptibility gene.
Fisher SA, Mirza MM, Onnie CM, Soars D, Lewis CM, Prescott NJ, Mathew CG, Sanderson J, Forbes A, Todhunter C, Donaldson P, Mansfield J
Gastroenterology. 2007 ; 132 (5) : 2078-2080.
PMID 17484911
 
TUCAN (CARD8) genetic variants and inflammatory bowel disease.
McGovern DP, Butler H, Ahmad T, Paolucci M, van Heel DA, Negoro K, Hysi P, Ragoussis J, Travis SP, Cardon LR, Jewell DP
Gastroenterology. 2006 ; 131 (4) : 1190-1196.
PMID 17030188
 
TUCAN, an antiapoptotic caspase-associated recruitment domain family protein overexpressed in cancer.
Pathan N, Marusawa H, Krajewska M, Matsuzawa S, Kim H, Okada K, Torii S, Kitada S, Krajewski S, Welsh K, Pio F, Godzik A, Reed JC
The Journal of biological chemistry. 2001 ; 276 (34) : 32220-32229.
PMID 11408476
 
CARD-8 protein, a new CARD family member that regulates caspase-1 activation and apoptosis.
Razmara M, Srinivasula SM, Wang L, Poyet JL, Geddes BJ, DiStefano PS, Bertin J, Alnemri ES
The Journal of biological chemistry. 2002 ; 277 (16) : 13952-13958.
PMID 11821383
 
TUCAN/CARDINAL and DRAL participate in a common pathway for modulation of NF-kappaB activation.
Stilo R, Leonardi A, Formisano L, Di Jeso B, Vito P, Liguoro D
FEBS letters. 2002 ; 521 (1-3) : 165-169.
PMID 12067710
 
A novel isoform of TUCAN is overexpressed in human cancer tissues and suppresses both caspase-8- and caspase-9-mediated apoptosis.
Yamamoto M, Torigoe T, Kamiguchi K, Hirohashi Y, Nakanishi K, Nabeta C, Asanuma H, Tsuruma T, Sato T, Hata F, Ohmura T, Yamaguchi K, Kurotaki T, Hirata K, Sato N
Cancer research. 2005 ; 65 (19) : 8706-8714.
PMID 16204039
 
NDPP1 is a novel CARD domain containing protein which can inhibit apoptosis and suppress NF-kappaB activation.
Zhang H, Fu W
International journal of oncology. 2002 ; 20 (5) : 1035-1040.
PMID 11956601
 

Citation

This paper should be referenced as such :
Kruyt, Frank A
CARD8 (caspase recruitment domain family, member 8)
Atlas Genet Cytogenet Oncol Haematol. 2007;11(4):294-296.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/CARD8ID913ch19q13.html


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 2 ]
  CARD8/BCKDHA (19q13)
CARD8/SULT2B1 (19q13)


External links

Nomenclature
Cards
AtlasCARD8ID913ch19q13.txt
Aliases
Genomic and cartography
Gene and transcription
RefSeq transcript (Entrez)
RefSeq genomic (Entrez)
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
BioGPS (Tissue expression)22900
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Protein Interaction databases
Ontologies - Pathways
Clinical trials, drugs, therapy
Miscellaneous
canSAR (ICR) (select the gene name)
Probes
Litterature
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed


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indexed on : Thu Oct 18 17:30:33 CEST 2018

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