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FDFT1  -  farnesyl-diphosphate farnesyltransferase 1

Homo sapiens

Synonyms: DGPT, ERG9, FPP:FPP farnesyltransferase, Farnesyl-diphosphate farnesyltransferase, SQS, ...
 
 
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Disease relevance of FDFT1

 

High impact information on FDFT1

  • Northern blot analysis showed overexpression of CTSB and FDFT1 mRNA in all six of the amplified esophageal adenocarcinomas analyzed [1].
  • Squalene synthetase activity in human fibroblasts: regulation via the low density lipoprotein receptor [6].
  • The human SQS (hSQS) gene has an unusually complex promoter with multiple binding sites for the sterol regulatory element binding proteins SREBP-1a and SREBP-2, and for accessory transcription factors known to be involved in the control of other sterol-responsive genes [7].
  • The two activities, presqualene pyrophosphate synthetase and squalene synthetase, copurified during isolation [8].
  • The differential effects of relatively thick monoglyceride bilayers on proton transfer in both dioxolane-linked gA channels must relate to distinct interactions between the bilayers and the SS and RR dioxolanes [9].
 

Biological context of FDFT1

  • Localization of the squalene synthase gene (FDFT1) to human chromosome 8p22-p23.1 [10].
  • Real-time PCR helped validate the downregulation of SREBF1, HMGCS1, FDFT1, and HSD3B4 genes [11].
  • By identifying sequences conserved between yeast SQS (ySQS) and PhS, we have cloned a 2-kb cDNA (hSQS) encoding human SQS, a protein of 417 amino acids with a predicted M(r) of 48,041, which has only limited homology to ySQS [2].
  • The ribulose 1,5-bisphosphate carboxylase/oxygenase small subunit (Rubisco SS) genes are of similar size (approximately 1.4 kb) to transgenes present in GM plants [12].
  • Children as a sensitive subgroup and their role in regulatory toxicology: DGPT workshop report [13].
 

Anatomical context of FDFT1

  • SQS is a membrane-bound enzyme in both T. cruzi epimastigotes and Leishmania mexicana promastigotes with a dual subcellular localization, being almost evenly distributed between glycosomes and mitochondrial/microsomal vesicles [14].
 

Associations of FDFT1 with chemical compounds

 

Other interactions of FDFT1

  • In particular, the SS and OSC genes were coordinately induced at 8 days of incubation, and their expression persisted throughout the incubation period [19].
  • The enzymes squalene synthetase, squalene epoxidase and oxidosqualene cyclase were identified as potential targets [20].
 

Analytical, diagnostic and therapeutic context of FDFT1

  • Chromatin immunoprecipitation also shows that SREBP-1a is recruited efficiently to Red and FAS promoters but not to SQS [21].
  • Squalene synthase (SQS, E.C. 2.5.1.21) catalyzes the first committed step in sterol biosynthesis and is currently under intense study as a possible target for cholesterol-lowering agents in humans, but it has not been investigated as a target for anti-parasitic chemotherapy [14].
  • Human serum albumin was separated to two forms by high-performance liquid chromatography: mercaptalbumin (SH type) and nonmercaptalbumin (SS type) [22].
  • Site-directed mutagenesis has identified conserved Asp, Tyr, and Phe residues that are essential for SQS activity [23].

References

  1. A novel amplicon at 8p22-23 results in overexpression of cathepsin B in esophageal adenocarcinoma. Hughes, S.J., Glover, T.W., Zhu, X.X., Kuick, R., Thoraval, D., Orringer, M.B., Beer, D.G., Hanash, S. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  2. Cloning, expression and characterisation of the cDNA encoding human hepatic squalene synthase, and its relationship to phytoene synthase. Summers, C., Karst, F., Charles, A.D. Gene (1993) [Pubmed]
  3. Dermatomyositis and drugs. Dourmishev, A.L., Dourmishev, L.A. Adv. Exp. Med. Biol. (1999) [Pubmed]
  4. Regulation of squalene synthetase in human hepatoma cell line Hep G2 by sterols, and not by mevalonate-derived non-sterols. Cohen, L.H., van Miert, E., Griffioen, M. Biochim. Biophys. Acta (1989) [Pubmed]
  5. Recently characterised autoantibodies and their clinical significance. Sturgess, A. Australian and New Zealand journal of medicine. (1992) [Pubmed]
  6. Squalene synthetase activity in human fibroblasts: regulation via the low density lipoprotein receptor. Faust, J.R., Goldstein, J.L., Brown, M.S. Proc. Natl. Acad. Sci. U.S.A. (1979) [Pubmed]
  7. Squalene synthase: structure and regulation. Tansey, T.R., Shechter, I. Prog. Nucleic Acid Res. Mol. Biol. (2001) [Pubmed]
  8. Squalene synthetase. Solubilization and partial purification of squalene synthetase, copurification of presqualene pyrophosphate and squalene synthetase activities. Kuswik-Rabiega, G., Rilling, H.C. J. Biol. Chem. (1987) [Pubmed]
  9. Proton transfer in gramicidin channels is modulated by the thickness of monoglyceride bilayers. Chernyshev, A., Armstrong, K.M., Cukierman, S. Biophys. J. (2003) [Pubmed]
  10. Localization of the squalene synthase gene (FDFT1) to human chromosome 8p22-p23.1. Schechter, I., Conrad, D.G., Hart, I., Berger, R.C., McKenzie, T.L., Bleskan, J., Patterson, D. Genomics (1994) [Pubmed]
  11. Transcriptional downregulation of sterol metabolism genes in murine liver exposed to acute hypobaric hypoxia. Dolt, K.S., Karar, J., Mishra, M.K., Salim, J., Kumar, R., Grover, S.K., Qadar Pasha, M.A. Biochem. Biophys. Res. Commun. (2007) [Pubmed]
  12. DNA stability in plant tissues: implications for the possible transfer of genes from genetically modified food. Chiter, A., Forbes, J.M., Blair, G.E. FEBS Lett. (2000) [Pubmed]
  13. Children as a sensitive subgroup and their role in regulatory toxicology: DGPT workshop report. Schwenk, M., Gundert-Remy, U., Heinemeyer, G., Olejniczak, K., Stahlmann, R., Kaufmann, W., Bolt, H.M., Greim, H., von Keutz, E., Gelbke, H.P. Arch. Toxicol. (2003) [Pubmed]
  14. Squalene synthase as a chemotherapeutic target in Trypanosoma cruzi and Leishmania mexicana. Urbina, J.A., Concepcion, J.L., Rangel, S., Visbal, G., Lira, R. Mol. Biochem. Parasitol. (2002) [Pubmed]
  15. Current, new and future treatments in dyslipidaemia and atherosclerosis. Chong, P.H., Bachenheimer, B.S. Drugs (2000) [Pubmed]
  16. On the origin of closing flickers in gramicidin channels: a new hypothesis. Armstrong, K.M., Cukierman, S. Biophys. J. (2002) [Pubmed]
  17. Inhibition of a plant sesquiterpene cyclase by mevinolin. Vögeli, U., Chappell, J. Arch. Biochem. Biophys. (1991) [Pubmed]
  18. The isoprenoid pathway in the ectomycorrhizal fungus Tuber borchii Vittad.: cloning and characterisation of the tbhmgr, tbfpps and tbsqs genes. Guidi, C., Zeppa, S., Annibalini, G., Pierleoni, R., Guescini, M., Buffalini, M., Zambonelli, A., Stocchi, V. Curr. Genet. (2006) [Pubmed]
  19. Upregulation of Isoprenoid Pathway Genes During Enhanced Saikosaponin Biosynthesis in the Hairy Roots of Bupleurum falcatum. Kim, Y.S., Cho, J.H., Ahn, J., Hwang, B. Mol. Cells (2006) [Pubmed]
  20. Squalene epoxidase as hypocholesterolemic drug target revisited. Chugh, A., Ray, A., Gupta, J.B. Prog. Lipid Res. (2003) [Pubmed]
  21. Selective association of sterol regulatory element-binding protein isoforms with target promoters in vivo. Bennett, M.K., Toth, J.I., Osborne, T.F. J. Biol. Chem. (2004) [Pubmed]
  22. Human serum albumin inhibits prostacyclin production by endothelial cells: the relation of the inhibitory activity to sulfhydryl groups in albumin. Murohara, Y., Yui, Y., Hattori, R., Kadota, K., Kawai, C. Jpn. Circ. J. (1991) [Pubmed]
  23. Structure and regulation of mammalian squalene synthase. Tansey, T.R., Shechter, I. Biochim. Biophys. Acta (2000) [Pubmed]
 
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