Alternative titles; symbols
HGNC Approved Gene Symbol: TRAF4
Cytogenetic location: 17q11.2 Genomic coordinates (GRCh38): 17:28,744,011-28,750,956 (from NCBI)
Tomasetto et al. (1995) identified genes, including TRAF4, that are overexpressed in breast cancer by differential screening of cDNAs from breast cancer-derived metastatic axillary lymph nodes.
Regnier et al. (1995) found that the TRAF4 gene, designated CART1 by them, encodes a deduced 470-amino acid protein that has an unusual RING finger motif at the N terminus, a cysteine-rich domain, called a CART motif, more centrally located, and a TRAF domain at the C terminus (see 601711). The authors reported that CART1 is expressed by epithelial cells only in breast carcinomas and metastases and that the protein is localized in the nucleus. They stated that CART1 appears to be involved in tumor necrosis factor (TNF)-related cytokine signal transduction in breast carcinoma.
Regnier et al. (1995) found that the TRAF4 gene spans approximately 5.5 kb and contains 7 exons.
Tomasetto et al. (1995) mapped the TRAF4 gene, which they called MLN62, to chromosome 17q11-q12 by radioisotopic in situ hybridization.
To investigate the biologic function of TRAF4, Regnier et al. (2002) generated Traf4-deficient mice by gene disruption. The mutation was embryonic lethal but with great individual variation, as approximately one-third of the homozygous embryos died in utero around embryonic day 14, whereas the others reached adulthood. Surviving mutant mice manifested numerous developmental abnormalities; notably, 100% of homozygous mutant mice suffered respiratory disorder and wheezing caused by tracheal ring disruption. Additional malformations concerned mainly the axial skeleton, as the ribs, sternum, tail, and vertebral arches were affected, with various degrees of penetrance. Traf4-deficient mice also exhibited a high incidence of spina bifida, a defect likened to neural tube defects (NTDs) that are common congenital malformations in humans. The results demonstrated that TRAF4 is required during embryogenesis in key biologic processes including the formation of the trachea, the development of the axial skeleton, and the closure of the neural tube. Considering the normal expression pattern of TRAF4 in neural tissues, Regnier et al. (2002) concluded that TRAF4 participates in neurulation in vivo.
Regnier, C. H., Masson, R., Kedinger, V., Textoris, J., Stoll, I., Chenard, M.-P., Dierich, A., Tomasetto, C., Rio, M.-C. Impaired neural tube closure, axial skeleton malformations, and tracheal ring disruption in TRAF4-deficient mice. Proc. Nat. Acad. Sci. 99: 5585-5590, 2002. Note: Erratum: Proc. Nat. Acad. Sci. 99: 8457 only, 2002. [PubMed: 11943846] [Full Text: https://doi.org/10.1073/pnas.052124799]
Regnier, C. H., Tomasetto, C., Moog-Lutz, C., Chenard, M.-P., Wendling, C., Basset, P., Rio, M.-C. Presence of a new conserved domain in CART1, a novel member of the tumor necrosis factor receptor-associated protein family, which is expressed in breast carcinoma. J. Biol. Chem. 270: 25715-25721, 1995. [PubMed: 7592751] [Full Text: https://doi.org/10.1074/jbc.270.43.25715]
Tomasetto, C., Regnier, C., Moog-Lutz, C., Mattei, M. G., Chenard, M. P., Lidereau, R., Basset, P., Rio, M. C. Identification of four novel human genes amplified and overexpressed in breast carcinoma and localized to the q11-q21.3 region of chromosome 17. Genomics 28: 367-376, 1995. [PubMed: 7490069] [Full Text: https://doi.org/10.1006/geno.1995.1163]