Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Patent
1995-01-13
1999-12-21
Carlson, Karen Cochrane
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
530300, 530350, C07H 1700, C07K 1400
Patent
active
060050861
ABSTRACT:
Farnesyl pyrophosphate, the metabolically active form of farnesol, is a key precursor in the synthesis of cholesterol, carotenoids, steroid hormones, bile acids and other molecules involved in cellular growth and metabolism. A nuclear receptor has been identified that is transcriptionally activated by farnesol and related molecules. This novel signaling pathway can be modulated by the use of key metabolic intermediates (or analogs and/or derivatives thereof) as transcriptional regulatory signals.
REFERENCES:
patent: 4209529 (1980-06-01), Tomiyama
patent: 4289786 (1981-09-01), Okabe et al.
patent: 5298655 (1994-03-01), Anthony et al.
patent: 5475029 (1995-12-01), Bradfute et al.
patent: 5571696 (1996-11-01), Evans et al.
patent: 5728548 (1998-03-01), Bowman
Seol et al., Mol. Endocrinol. 9(1), 72-85 (Jan. 1995).
Bradley et al., ".alpha. and .beta. thyroid hormone receptor (TR) gene expression during auditory neurogenesis: Evidence for TR isoform-specific transcriptional regulation in vivo" Proc. Natl. Acad. Sci. USA 91:439-443 (1994).
Brown and Goldstein, "Multivalent feedback regulation of HMG CoA reductase, a control mechanism coordinating isoprenoid synthesis and cell growth" J. Lipid Res. 21:505-517 (1980).
Danciger et al., "A Second Mouse Glutamic Acid Decarboxylase gene (Gad-2) Maps Proximal to Gad-1 on Chromosome 2" Mouse Genome 91:320-322 (1993).
Danielian et al., "Identification of a conserved region required for hormone dependent transcriptional activation by steroid hormone receptors" EMBO J. 11:1025-1033 (1992).
Edmond et al., "Mevalonate Metabolism: Role of Kidneys" Science 193:154-156 (1976).
Evans, "The Steroid and Thyroid Hormone Receptor Superfamily" Science 240:889-895 (1988).
Forman and Samuels, "Interactions Among a Subfamily of Nuclear Hormone Receptors: The Regulatory Zipper Model" Mol. Endocrinol. 4:1293-1301 (1990).
Glass, "Differential Recognition of Target Genes by Nuclear Receptor Monomers, Dimers, and Heterodimers" Endocr. Rev. 15:391-407 (1994).
Goldstein and Brown, "Regulation of the mevalonate pathway" Nature 343:425-430 (1990).
Gomez et al., "Purified yeast protein farnesyltransferase is structurally and functionally similar to its mammalian counterpart" Biochem. J. 289:25-31 (1993).
Gottlicher et al., "Fatty acids activate a chimera of the clofibric acid-activated receptor and the glucocorticoid receptor" Proc. Natl. Acad. Sci. USA 89:4653-4657 (1992).
Green and Wahli, "Peroxisome proliferator-activated receptors: finding the orphan a home" Mol. Cell Endocrinol. 100:149-153 (1994).
Hallenbeck et al., "Heterodimerization of thyroid hormone (TH) receptor with H-2RIIBP (RXR.beta.) enhances DNA binding and TH-dependent transcriptional activation" Proc. Natl. Acad. Sci. USA 89:5572-5576 (1992).
Heyman et al., "9-Cis Retinoic Acid Is a High Affinity Ligand for the Retinoid X Receptor" Cell 68:397-406 (1992).
Issemann and Green, "Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators" Nature 347:645-650 (1990).
Kensler et al., "Effects of Retinoic Acid and Juvenile Hormone on the Induction of Ornithine Decarboxylase Activity by 12-O-Tetradecanoylphorbol-13-acetate.sup.1 " Cancer Res. 38:2896-2899 (1978).
Kim et al., "cDNA Cloning of MEV, a Mutant Protein That Facilitates Cellular Uptake of Mevalonate, and Identification of the Point Mutation Responsible for Its Gain of Function" J. Biol. Chem. 267:23223-23121 (1992).
Kliewer et al., "Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D.sub.3 signalling" Nature 355:446-449 (1992).
Kurokawa et al., "Regulation of retinoid signalling by receptor polarity and allosteric control of ligand binding" Nature 371:528-531 (1994).
Leid et al., "Purification, Cloning, and RXR Identity on the HeLa Cell Factor with Which RAR or TR Heterodimerizes to Bind Target Sequences Efficiently" Cell 68:377-395 (1992).
Levin et al., "9-Cis retinoic acid stereoisomer binds and activates the nuclear receptor RXR.alpha." Nature 355:359-361 (1992).
Mangelsdorf et al., "Characterization of three RXR genes that mediate the action of 9-cis retinoic acid" Genes Dev. 6:329-344 (1992).
Marks et al., "H-2RIIBP (RXR.beta.) heterodimerization provides a mechanism for combinatorial diversity in the regulation of retinoic acid and thyroid hormone responsive genes" EMBO J. 11:1419-1435 (1992).
Nagpal et al., "RARs and RXRs: evidence for two autonomous transactivation functions (AF-1 and AF-2) and heterodimerization in vivo" EMBO J. 12:2349-2360 (1993).
Nakanishi et al., "Multivalent Control of 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase" J. Biol. Chem. 263:8929-8937 (1988).
O'Malley, "Editorial: Did Eucaryotic Steroid Receptors Evolve from Intracrine Gene Regulators?" Endocrinology 125:1119-1120 (1989).
Reiss et al., "Inhibition of Purified p21.sup.ras Farnesyl:Protein Transferase by Cys-AAX Tetrapeptides" Cell 62:81-88 (1990).
Righetti et al., "The in Vitro Metabolism of Mevalonate by Sterol and Non-sterol Pathways" J. Biol. Chem. 251:2716-2721 (1976).
Sunada et al., "Deficiency of Merosin in Dystrophic dy Mice and Genetic Linkage of Laminin M Chain Gene to dy Locus" J. Biol. Chem. 269:13729-13732 (1994).
Sutcliffe et al., "Control of Neuronal Gene Expression" Science 225:1308-1315 (1984).
Sze et al., "In Vitro Transcriptional Activation by a metabolic Intermediate: Activation by Leu3 Depends on .alpha.-Isopropylmalate" Science 258:1143-1145 (1992).
Thomas et al., "Heterodimerization of the Drosophila ecdysone receptor with retinoid X receptor and ultraspiracle" Nature 362:471-475 (1993).
Tomkins, "The Metabolic Code" Science 189:760-763 (1975).
Tontonoz et al., "mPPAR.gamma.2: tissue-specific regulator of an adipocyte enhancer" Genes Dev. 8:1224-1234 (1994).
Wang et al., "SREBP-1, a Membrane-Bound Transcription Factor Released by Sterol-Regulated Proteolysis" Cell 77:53-62 (1994).
Wiley et al., "The Quantitative Role of the Kidneys in the in Vivo Metabolism of Mevalonate" J. Biol. Chem. 252:548-554 (1977).
Yao et al., "Drosophila ultraspiracle Modulates Ecdysone Receptor Function via Heterodimer Formation" Cell 71:63-72 (1992).
Yao et al., "Functional ecdysone receptor is the product of EcR and Ultraspiracle genes" Nature 366:476-479 (1993).
Yu et al., "RXR.beta.: A Coregulator That Enhances Binding of Retinoic Acid, Thyroid Hormone, and Vitamin D Receptors to Their Cognate Response Elements" Cell 67:1251-1266 (1991).
Zhang et al., "Retinoid X receptor is an auxiliary protein for thyroid hormone and retinoic acid receptors" Nature 355:441-446 (1992).
Bradfute et al., "Non-sterol Compounds That Regulate cholesterogenesis" J. Biol. Chem. 269(9):6645-6650 (1994).
Corsini et al., "Relationship Between mevalonate Pathway and Arterial Myocyte Proliferation: In Vitro Studies with Inhibitors of HMG-CoA Reductase" Atherosclerosis 101:117-125 (1993).
Fioravanti et al., "The In Vitro Effects of Farnesol and Derivatives on Hymenolepis Diminuta" J. Parasitol. 62(5):749-755 (1976).
Forman et al., "Identification of a Nuclear Receptor That Is Activated by Farnesol Metabolites" Cell 81:687-693 (1995).
Weinberger, "A Model for Farnesoid Feedback Control in the Mevalonate Pathway" Trends in Endocrinol. and Metabolism 7(1):1-6 (1996).
Forman et al., Cell 81, 687-693 (Jun. 2, 1995).
Forman et al., J. Inv. Med. 43(Suppl. 2), 1995 Abstract. 380A.
Evans Ronald M.
Forman Barry M.
Weinberger Cary A.
Carlson Karen Cochrane
Reiter Stephen E.
The Salk Institute for Biological Studies
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