Oxysterols are allosteric activators of the oncoprotein Smoothened (original) (raw)

• Varjosalo, M. & Taipale, J. Hedgehog: functions and mechanisms. Genes Dev. 22, 2454–2472 (2008).
  Article CAS Google Scholar
• Murone, M., Rosenthal, A. & de Sauvage, F.J. Sonic hedgehog signaling by the patched-smoothened receptor complex. Curr. Biol. 9, 76–84 (1999).
  Article CAS Google Scholar
• Stone, D.M. et al. The tumour-suppressor gene patched encodes a candidate receptor for Sonic hedgehog. Nature 384, 129–134 (1996).
  Article CAS Google Scholar
• Marigo, V. et al. Biochemical evidence that patched is the Hedgehog receptor. Nature 384, 176–179 (1996).
  Article CAS Google Scholar
• Barakat, M.T., Humke, E.W. & Scott, M.P. Learning from Jekyll to control Hyde: Hedgehog signaling in development and cancer. Trends Mol. Med. 16, 337–348 (2010).
  Article CAS Google Scholar
• Cooper, M.K., Porter, J.A., Young, K.E. & Beachy, P.A. Teratogen-mediated inhibited of target tissue response to Shh signaling. Science 280, 1603–1607 (1998).
  Article CAS Google Scholar
• Chen, J.K. et al. Inhibition of Hedgehog signaling by direct binding of cyclopamine to Smoothened. Genes Dev. 16, 2743–2748 (2002).
  Article CAS Google Scholar
• Heretsch, P., Tzagkaroulaki, L. & Giannis, A. Cyclopamine and hedgehog signaling: chemistry, biology, medical perspectives. Angew. Chem. Int. Ed. Engl. 49, 3418–3427 (2010).
  Article CAS Google Scholar
• Chen, J.K. et al. Small molecule modulation of Smoothened activity. Proc. Natl. Acad. Sci. USA 99, 14071–14076 (2002).
  Article CAS Google Scholar
• Sinha, S. & Chen, J.K. Purmorphamine activates the Hedgehog pathway by targeting Smoothened. Nat. Chem. Biol. 2, 29–30 (2006).
  Article CAS Google Scholar
• Romer, J.T. et al. Suppression of the Shh pathway using a small molecule inhibitor eliminates medulloblastoma in Ptc1+/−p53−/− mice. Cancer Cell 6, 229–240 (2004).
  Article CAS Google Scholar
• Corcoran, R.B. & Scott, M.P. Oxysterols stimulate Sonic hedgehog signal transduction and proliferation of medulloblastoma cells. Proc. Natl. Acad. Sci. USA 103, 8408–8413 (2006).
  Article CAS Google Scholar
• Dwyer, J.R. et al. Oxysterols are novel activators of the hedgehog signaling pathway in pluripotent mesenchymal cells. J. Biol. Chem. 282, 8959–8968 (2007).
  Article CAS Google Scholar
• Johnson, J.S. et al. Novel oxysterols have pro-osteogenic and anti-adipogenic effects in vitro and induce spinal fusion in vivo. J. Cell Biochem. 112, 1673–1684 (2011).
  Article CAS Google Scholar
• Rohatgi, R., Milenkovic, L. & Scott, M.P. Patched1 regulates hedgehog signaling at the primary cilium. Science 317, 372–376 (2007).
  Article CAS Google Scholar
• Corbit, K.C. et al. Vertebrate Smoothened functions at the primary cilium. Nature 437, 1018–1021 (2005).
  Article CAS Google Scholar
• LeBlanc, M.A. & McMaster, C.R. Lipid binding requirements for oxysterol-binding protein Kes1 inhibition of autophagy and endosome-trans-Golgi trafficking pathways. J. Biol. Chem. 285, 33875–33884 (2010).
  Article CAS Google Scholar
• Radhakrishnan, A. et al. Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi: oxysterols block transport by binding to Insig. Proc. Natl. Acad. Sci. USA 104, 6511–6518 (2007).
  Article CAS Google Scholar
• Janowski, B.A. et al. Structural requirements of ligands for the oxysterol liver X receptors LXRα and LXRβ. Proc. Natl. Acad. Sci. USA 96, 266–271 (1999).
  Article CAS Google Scholar
• Chen, W. et al. Enzymatic reduction of oxysterols impairs LXR signaling in cultured cells and the livers of mice. Cell Metab. 5, 73–79 (2007).
  Article CAS Google Scholar
• Hannedouche, S. et al. Oxysterols direct immune cell migration via EBI2. Nature 475, 524–527 (2011).
  Article CAS Google Scholar
• Liu, C. et al. Oxysterols direct B-cell migration through EBI2. Nature 475, 519–523 (2011).
  Article CAS Google Scholar
• Panini, S.R. & Sinensky, M.S. Mechanisms of oxysterol-induced apoptosis. Curr. Opin. Lipidol. 12, 529–533 (2001).
  Article CAS Google Scholar
• Park, K. & Scott, A.L. Cholesterol 25-hydroxylase production by dendritic cells and macrophages is regulated by type I interferons. J. Leukoc. Biol. 88, 1081–1087 (2010).
  Article CAS Google Scholar
• Theunissen, J.J. et al. Membrane properties of oxysterols. Interfacial orientation, influence on membrane permeability and redistribution between membranes. Biochim. Biophys. Acta 860, 66–74 (1986).
  Article CAS Google Scholar
• Rentero, C. et al. Functional implications of plasma membrane condensation for T cell activation. PLoS ONE 3, e2262 (2008).
  Article Google Scholar
• Olkkonen, V.M. & Hynynen, R. Interactions of oxysterols with membranes and proteins. Mol. Aspects Med. 30, 123–133 (2009).
  Article CAS Google Scholar
• Sasaki, H. et al. A binding site for Gli proteins is essential for HNF-3β floor plate enhancer activity in transgenics and can respond to Shh in vitro. Development 1997, 1313–1322 (1997).
  Google Scholar
• Infante, R.E. et al. Purified NPC1 protein. I. Binding of cholesterol and oxysterols to a 1278-amino acid membrane protein. J. Biol. Chem. 283, 1052–1063 (2008).
  Article CAS Google Scholar
• Massey, J.B. & Pownall, H.J. Structures of biologically active oxysterols determine their differential effects on phospholipid membranes. Biochemistry 45, 10747–10758 (2006).
  Article CAS Google Scholar
• Covey, D.F. ent-Steroids: novel tools for studies of signaling pathways. Steroids 74, 577–585 (2009).
  Article CAS Google Scholar
• Mannock, D.A. et al. Effects of natural and enantiomeric cholesterol on the thermotropic phase behavior and structure of egg sphingomyelin bilayer membranes. Biophys. J. 84, 1038–1046 (2003).
  Article CAS Google Scholar
• Westover, E.J. et al. Cholesterol depletion results in site-specific increases in epidermal growth factor receptor phosphorylation due to membrane level effects. Studies with cholesterol enantiomers. J. Biol. Chem. 278, 51125–51133 (2003).
  Article CAS Google Scholar
• Gale, S.E. et al. Side chain oxygenated cholesterol regulates cellular cholesterol homeostasis through direct sterol-membrane interactions. J. Biol. Chem. 284, 1755–1764 (2009).
  Article CAS Google Scholar
• Rominger, C.M. et al. Evidence for allosteric interactions of antagonist binding to the smoothened receptor. J. Pharmacol. Exp. Ther. 329, 995–1005 (2009).
  Article CAS Google Scholar
• Kenakin, T.P. A Pharmacology Primer. 3rd edn. 101–147 (Elsevier, 2009).
• Kim, J. et al. Itraconazole, a commonly used antifungal that inhibits Hedgehog pathway activity and cancer growth. Cancer Cell 17, 388–399 (2010).
  Article CAS Google Scholar
• Fitzgerald, J.B. et al. Systems biology and combination therapy in the quest for clinical efficacy. Nat. Chem. Biol. 2, 458–466 (2006).
  Article CAS Google Scholar
• Rohatgi, R. et al. Hedgehog signal transduction by Smoothened: pharmacologic evidence for a 2-step activation process. Proc. Natl. Acad. Sci. USA 106, 3196–3201 (2009).
  Article CAS Google Scholar
• Töröcsik, D., Szanto, A. & Nagy, L. Oxysterol signaling links cholesterol metabolism and inflammation via the liver X receptor in macrophages. Mol. Aspects Med. 30, 134–152 (2009).
  Article Google Scholar
• Brown, A.J. Cholesterol, statins and cancer. Clin. Exp. Pharmacol. Physiol. 34, 135–141 (2007).
  Article CAS Google Scholar
• Cooper, M.K. et al. A defective response to Hedgehog signaling in disorders of cholesterol biosynthesis. Nat. Genet. 33, 508–513 (2003).
  Article CAS Google Scholar
• Lin, Y.Y., Welch, M. & Lieberman, S. The detection of 20S-hydroxycholesterol in extracts of rat brains and human placenta by a gas chromatograph/mass spectrometry technique. J. Steroid Biochem. Mol. Biol. 85, 57–61 (2003).
  Article CAS Google Scholar
• Mijares, A. et al. Studies on the C20 epimers of 20-hydroxycholesterol. J. Org. Chem. 32, 810–812 (1967).
  Article CAS Google Scholar
• Ruprecht, J.J. et al. Electron crystallography reveals the structure of metarhodopsin I. EMBO J. 23, 3609–3620 (2004).
  Article CAS Google Scholar
• Cherezov, V. et al. High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor. Science 318, 1258–1265 (2007).
  Article CAS Google Scholar
• Roberts, K.D., Bandy, L. & Lieberman, S. The occurrence and metabolism of 20 alpha-hydroxycholesterol in bovine adrenal preparations. Biochemistry 8, 1259–1270 (1969).
  Article CAS Google Scholar
• Lütjohann, D. et al. Cholesterol homeostasis in human brain: evidence for an age-dependent flux of 24S-hydroxycholesterol from the brain into the circulation. Proc. Natl. Acad. Sci. USA 93, 9799–9804 (1996).
  Article Google Scholar