Alternative titles; symbols
HGNC Approved Gene Symbol: THRSP
Cytogenetic location: 11q14.1 Genomic coordinates (GRCh38) : 11:78,063,861-78,068,351 (from NCBI)
Expression of the rat and mouse Spot14 (S14) gene has been extensively studied in liver and adipose tissue in which its regulation is under the intricate control of several nutritional and hormonal factors (Clarke et al., 1990; Jump et al., 1994; Liu and Towle, 1994). S14 has been implicated in lipogenesis. Moreover, its expression is altered in streptozotocin-induced diabetes. Grillasca et al. (1997) cloned the human gene (symbolized THRSP, for 'thyroid hormone-responsive Spot14 homolog') and found that it has the same organization as the rat gene and predicts a highly conserved amino acid sequence (more than 80%). The THRSP gene is expressed in human liver and adipocytes, particularly in lipomatous nodules.
Taviaux et al. (1997) mapped the THRSP gene to chromosome 11q13.5-q14.1 by fluorescence in situ hybridization. Durkin et al. (1994) tentatively mapped the 'Spot 14' gene to the human X chromosome. By fluorescence in situ hybridization, however, Moncur et al. (1997) mapped the THRSP gene to 11q13.5, thus confirming the assignment by Taviaux et al. (1997).
Enhanced long-chain fatty acid synthesis may occur in breast cancer, where it is necessary for tumor growth and predicts a poor prognosis. The S14 protein functions to activate genes encoding the enzymes of fatty acid synthesis. Amplification of chromosome region 11q13, where the THRSP gene resides, also predicts a poor prognosis in breast tumors. Moncur et al. (1998) localized the THRSP gene between markers D11S906 and D11S937, at the telomeric end of the amplified region at 11q13, and found that it was amplified and expressed in breast cancer-derived cell lines. Other findings supported a role for the protein as a determinant of tumor lipid metabolism. Expression of S14 provided a pathophysiologic link between 2 prognostic indicators in breast cancer: enhanced lipogenesis and 11q13 amplification.
Knobloch et al. (2013) demonstrated that fatty acid synthase (FASN; 600212), the key enzyme of de novo lipogenesis, is highly active in adult neural stem and progenitor cells (NSPCs) and that conditional deletion of Fasn in mouse NSPCs impairs adult neurogenesis. The rate of de novo lipid synthesis and subsequent proliferation of NSPCs is regulated by Spot14 (601926), a gene implicated in lipid metabolism, that Knobloch et al. (2013) found to be selectively expressed in low proliferating adult NSPCs. Spot14 reduces the availability of malonyl-CoA, which is an essential substrate for Fasn to fuel lipogenesis. Knobloch et al. (2013) concluded that they identified a functional coupling between the regulation of lipid metabolism and adult NSPC proliferation.
Clarke, S. D., Armstrong, M. K., Jump, D. B. Nutritional control of rat liver fatty acid synthase and S14 mRNA abundance. J. Nutr. 120: 218-224, 1990. [PubMed: 2313386] [Full Text: https://doi.org/10.1093/jn/120.2.218]
Durkin, A. S., Nierman, W. C., Zoghbi, H., Jones, C., Kozak, C. A., Maglott, D. R. Chromosome assignment of human brain expressed sequence tags (ESTs) by analyzing fluorescently labeled PCR products from hybrid cell panels. Cytogenet. Cell Genet. 65: 86-91, 1994. [PubMed: 8404072] [Full Text: https://doi.org/10.1159/000133606]
Grillasca, J. P., Gastaldi, M., Khiri, H., Dace, A., Peyrol, N., Reynier, P., Torresani, J., Planells, R. Cloning and initial characterization of human and mouse Spot 14 genes. FEBS Lett. 401: 38-42, 1997. [PubMed: 9003802] [Full Text: https://doi.org/10.1016/s0014-5793(96)01433-0]
Jump, D. B., Clarke, S. D., Thelen, A., Liimatta, M. Coordinate regulation of glycolytic and lipogenic gene expression by polyunsaturated fatty acids. J. Lipid Res. 35: 1076-1084, 1994. [PubMed: 8077846]
Knobloch, M., Braun, S. M. G., Zurkirchen, L., von Schoultz, C., Zamboni, N., Arauzo-Bravo, M. J, Kovacs, W. J., Karalay, O., Suter, U., Machado, R. A. C., Roccio, M., Lutolf, M. P., Semenkovich, C. F., Jessberger, S. Metabolic control of adult neural stem cell activity by Fasn-dependent lipogenesis. Nature 493: 226-230, 2013. [PubMed: 23201681] [Full Text: https://doi.org/10.1038/nature11689]
Liu, H. C., Towle, H. C. Functional synergism between multiple thyroid hormone response elements regulates hepatic expression of the rat S14 gene. Molec. Endocr. 8: 1021-1037, 1994. [PubMed: 7997231] [Full Text: https://doi.org/10.1210/mend.8.8.7997231]
Moncur, J. T., Park, J. P., Maloney, M., Mohandas, T. K., Kinlaw, W. B. Assignment of the 'Spot 14' gene (THRSP) to human chromosome band 11q13.5 by in situ hybridization. Cytogenet. Cell Genet. 78: 131-132, 1997. [PubMed: 9371405] [Full Text: https://doi.org/10.1159/000134644]
Moncur, J. T., Park, J. P., Memoli, V. A., Mohandas, T. K., Kinlaw, W. B. The 'Spot 14' gene resides in the telomeric end of the 11q13 amplicon and is expressed in lipogenic breast cancers: implications for control of tumor metabolism. Proc. Nat. Acad. Sci. 95: 6989-6994, 1998. [PubMed: 9618526] [Full Text: https://doi.org/10.1073/pnas.95.12.6989]
Taviaux, S., Planells, R., Gastaldi, M., Torresani, J., Grillasca, J. P. Assignment of thyroid hormone responsive SPOT 14 homolog (THRSP) to human chromosome 11 bands q13.5-q14.1 by in situ hybridization. Cytogenet. Cell Genet. 76: 219-220, 1997. [PubMed: 9186528] [Full Text: https://doi.org/10.1159/000134553]