Abstract
A number of diverse chemical agents have been identified which perturb microtubule assembly and disassembly by interacting specifically with microtubule protein. Microtubules are found in all eukaryotic cells and are a major component of the mitotic spindle. Drugs that perturb microtubule polymerization and depolymerization in many cases are potent antimitotic agents with potential in cancer chemotherapy. In this chapter we review the pharmacology of a number of antimicrotubule drugs with emphasis on the mechanisms by which they alter microtubule function. To keep the review tractable, as the list of antimicrotubule agents is large, we confined ourselves primarily to the following drugs: colchicine and its derivatives; podophyllotoxins and nocodazole (competitive inhibitors of colchicine); the vinca alkaloids (e.g. vinblastine and vincristine); the macrolides (e.g., maytansine); taxol; and griseofulvin. These drugs were chosen, in part, because they illustrate different mechanisms of assembly inhibition. Furthermore, most of these drugs have been found to be effective in cancer chemotherapy and many are in clinical use. Our review benefited from a number of excellent earlier reviews (see references [1–4]).
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References
Dustin P: Microtubule Poisons. In: Microtubules, Springer-Verlag Publishers, 1978, p 166–225.
Luduena RF: Biochemistry of tubulin. In: Microtubules, Roberts K, Hyams J (eds), Academic Press, 1979, p 66–116.
Schiff P, Horwitz S: Tubulin, a target for chemotherapeutic agents. In: Molecular action and targets for cancer chemotherapeutic agents, Academic Press, 1980, p 483–505.
Kirschner M: Microtubule assembly and nucleation. In: International Review of Cytology, Vol. 54, Bourne G, Danielli J (eds), 1978, p 1–71.
Amos L: Arrangement of high molecular weight associated proteins on purified mammalian brain microtubules. J Cell Biol 72: 642–654, 1977.
Kim H, Binder L, Rosenbaum J: The periodic association of MAP2 with brain microtubules in vivo. J Cell Biol 80: 266–276, 1979.
Mendelkow E, Thomas J, Cohen H: Microtubule structure at low resolution by X-ray diffraction. Proc Natl Acad Sci USA 74: 3370–3374, 1977.
Pierson G, Burton P, Himes R: Alterations in number of proto-filaments in microtubules assembled in vitro. J Cell Biol 76: 223–228, 1978.
Taylor E: The mechanism of colchicine inhibition of mitosis. I. Kinetics of inhibition and the binding of H3–colchicine. J Cell Biol 25: 145–160, 1965.
Murphy D, Borisy G: Association of high-molecular-weight proteins with microtubules and their role in microtubule assembly. Proc Natl Acad Sci USA 72: 2696–2700, 1975.
Sloboda R, in vitroDentler W, Rosenbaum J: Microtubule-associated proteins and the stimulation of tubulin assembly. Biochemistry 15:4497–4505, 1976.
Bryan J, Wilson L: Are cytoplasmic microtubules heteropolymers? Proc Natl Acad Sci USA 8: 1762–1766, 1971.
Luduena R, Shooter E, Wilson L: Structure of the tubulin dimer. J Biol Chem 252: 7006–7014, 1977.
Erickson H: Microbutule surface lattice and subunit structure and observations on reassembly. J Cell Biol 60: 153–167, 1974.
Amos L, Baker T: The three–dimensional structure of tubulin protofilaments. Nature 279: 607–612, 1979.
Bergen L, Kuriyama R, Borisy G: Polarity of microtubules nucleated by centrosomes and chromosomes of Chinese hamster ovary cells in vitro. J Cell Biol 84: 151–159, 1980.
Heidemann S, Mcintosh J: Visualization of the structural polarity of microtubules. Nature 286: 517–519, 1980.
Kirschner M: Implications of treadmilling for the stability and polarity of actin and tubulin polymers in vivo. J Cell Biol 86: 330–334, 1980.
Nagle B, Doenges K, Bryan J: Assembly of tubulin from cultured cells and comparison with the neurotubulin model. Cell 12: 573–586, 1977.
Sherline P, Schiavona K: Immunofluorescence localization of proteins of high molecular weight along intracellular microtubules. Science 198: 1038–1040, 1977.
Cleveland D, Spiegelman M, Kirschner M: Conservation of microtubule associated proteins. J Biol Chem 254: 12670–12678, 1979.
Lee J, Tweedy N, Tinasheff S: In vitro reconstitution of calf brain microtubules: effects of macromolecules. Biochemistry 17: 2783–2790, 1978.
Cleveland D, Hwo S, Kirschner M: Purification of tau, a microtubule–associated protein that induces assembly of microtubules from purified tubulin. J Mol Biol 116: 207–225, 1977.
Murphy D, Johnson K, Borisy G: Role of tubulin-associated proteins in microtubule nucleation and elongation. J Mol Biol 117: 33–52, 1977.
Luduena R, Woodward O: α- and β-tubulin separation and partial sequence Ann NY Acad Sci 253: 272–283, 1975.
Luduena R, Woodward D: Isolation and partial characterization of α- and β-tubulin from outer doublets of sea urchin sperm and microtubules of chick-embryo brain. Proc Natl Acad Sci USA 70: 3594–3598, 1973.
Lu R, Elzinga M: Chromatographic resolution of the subunits of calf brain tubulin. Anal Biochem 77: 243–250, 1977.
Lu R, Elzinga M: The primary structure of tubulin sequences of the carboxyl terminus and seven other cyanogen bromide peptides from the α-chain. Biochim Biophys Acta 537:320– 328, 1978.
Ponstingl H, Little M, Krauhs E, Kempf T: Carboxy-terminal amino acid sequence of α-tubulin from porcine brain. Nature 282: 423–424, 1979.
Cleveland D, Fischer S, Kirschner M, Laemmli U: Peptide by limited proteolysis in sodium dodecyl sulfate and analysis by gel electrophoresis. J Biol Chem 252: 1102–1106, 1977.
Piperno G, Luck D: Microtubular proteins of Chlamydomonas reinhardtii. J Biol Chem 252: 383–391, 1977.
Cleveland D, Lopata M, MacDonald K, Cowan N, Rutter W, Kirschner M: Number and evolutionary conservation of α– and α–tubulin and cytoplasmic β– and α–actin genes using specific cloned cDNA probes. Cell 20: 95–105, 1980.
Krauhs E, Little M, Ade W, Kempf T, Hoter Warbinek R, Ponstingl H: 45% homology in the N-terminal 90 amino acid residues of α- and β-tubulin from porcine brain. In: Programme abstracts, 2nd international symposium on microtubules and microtubule inhibitors, Beerse (Belgium), p 63, 1980.
Valenzuela P, Quiroga M, Zaldivar J, Rutter W, Kirschner M, Cleveland D: Nucleotide and corresponding amino acid sequences encoded by α- and β-tubulin mRNAs. Nature 289: 650–656, 1981.
Stephens R: Primary structural differences among tubulin subunits from flagella, cilia and the cytoplasm. Biochemistry 17: 2882–2891, 1978.
Gozes R, Littauer U: Tubulin microheterogeneity increases with rat brain maturation. Nature 276: 411–413, 1978.
Barnstable C, Gozes I: Monoclonal antibodies that recognize discrete forms of tubulin. J Cell Biol 87: 251a, 1980.
Eipper B: Rat brain microtubule protein: purification and determination of covalently bound phosphate and carbohydrate. Proc Natl Acad Sci USA 69: 2283–2287, 1972.
Lockwood A: Cyclic nucleotide dependent protein kinase as molecular regulators of cell morphology. In: Microtubules and microtubule inhibitors, De Brabander M, De Mey J (eds), Elsevier press, 1980, p 71–83.
Margolis RK, Margolis RU, Shelanski M: The carbohydrate composition of brain microtubule protein. Biochem Biophys Res Commun 47: 432–437, 1972.
Raybin K, Flavin M: An enzyme tyrosylating β-tubulin and its role in microtubule assembly. Biochem Biophys Res Commun 65: 1088–1095, 1975.
Thompson W, Deanin G, Gordon M: Intact microtubules are required for rapid turnover of carboxyl–terminal tyrosine of β-tubulin in cell culture. Proc Natl Acad Sci USA 76: 1318–1322, 1979.
Crepeau R, McEwen B, Edelstein J: Differences in a and/polypeptide chains of tubulin resolved by electron microscopy with image reconstruction. Proc Natl Acad Sci USA 75: 5006–5010, 1978.
Ventilla M, Cantor C, Shelanski M: A circular dichroism study of microtubule protein. Biochemistry 11: 1554–1561, 1972.
Lee J, Frigon R, Tinasheff S: Structural stability of calf brain microtubule protein. Ann NY Acad Sci 253: 284–291, 1975.
Ringel I, Sternlicht H: A study of tubulin flexibility and conformation. Fed Proc (in press), June 1981.
Ponstingl H, Little M, Krauhs E, Kempf T: Microheterogeneity in the amino acid sequence of the C-terminal 200 positions in α–tubulin from porcine brain. In: Programme abstracts, 2nd international symposium on microtubules and microtubule inhibitors, Beerse (Belgium), p 29, 1980.
Lee Y, Houston L, Himes R: Inhibition of the self-assembly of tubulin by diethylpyrocarbonate and photooxidation. Biochem Biophys Res Commun 70: 50–57, 1976.
Kuriyama R: Further studies on tubulin polymerization in vitro. J Biochem (Tokyo) 77: 23–31, 1975.
Nishidi E, Kobagashi T: Relationship between tubulin SH groups and bound guanine nucleotide. J Biochem (Tokyo) 81: 343–347, 1977.
Sternlicht H, Ringel I, Szasz J, Burns R, Sherman G: Evidence for an essential lysine in microtubule assembly. J Cell Biol 87: 251a, 1980.
Sentein P: Action of gluteraldehyde and formaldehyde on segmentation mitosis. Exp Cell Res 95: 223–246, 1975.
Olmsted J, Borisy G: Ionic and nucleotide requirements for microtubule polymerization in vitro. Biochemistry 14: 2996–3005, 1975.
Solomon F: Binding sites for calcium on tubulin. Biochemistry 16: 358–36, 1977.
Gaskin F: In vitro microtubule assembly regulation by divalent cations and nucleotides. Biochemistry 20:1318–1322, 1981.
Weisenberg R: Microtubule formation in vitro in solutions containing low calcium concentrations. Science 177: 1104–1105, 1972.
Welsh M, Dedman J, Brinkley B, Means R: Calcium–dependent regulator protein: localization in mitotic apparatus of eukaryiotic cells. Proc Natl Acad Sci USA 75: 1867–1871, 1978.
Gaskin F, Kress Y: Zinc ion-induced assembly of tubulin. J Biol Chem 252: 6918–6924, 1977.
Weisenberg R, Borisy G, Taylor E: The colchicine-binding protein of mammalian brain and its relation to microtubules. Biochemistry 7: 4466–4479, 1968.
Bryan J: Definition of three classes of binding sites in isolated microtubule crystals. Biochemistry 11: 2611–2616, 1972.
Jameson L, Caplow M: Effect of guanosine diphosphate on microtubule assembly and stability. J Biol Chem 255: 2284–2292, 1980.
Weisenberg R, Deery W, Dickinson P: Tubulin-nucleotide interactions during the poly¬merization and depolymerization of microtubules. Biochemistry 15: 4248–4254, 1976.
Carlier M, Pantaloni D: Kinetic analysis of the correlation between tubulin assembly and GTP hydrolysis. In: Programme abstracts, 2nd international symposium on microtubule inhibitors, Beerse (Belgium), p 38, 1980.
Jacobs M: Tubulin and nucleotides. In: Microtubules, Roberts K, Hyams J (eds), Academic Press, 1979, p 255–277.
Gaskin F, Cantor R, Shelanski M: Turbidimetric studies of the in vitro assembly and disassembly of porcine neurotubules. J Mol Biol 89: 737–758, 1974.
Kuriyama R, Sakai H: Viscometric demonstration of tubulin polymerization. J Biochem (Tokyo) 75: 463–471, 1974.
Miki–Noumura T, Kamiya R: Shape of microtubules in solution. Exp Cell Res 97:451– 453, 1976.
Kirschner M, Honig L, Williams R: Quantitative electron microscopy of microtubule assembly in vitro. J Mol Biol 99: 263–276, 1975.
Berne B: Interpretation of the light scattering from long rods. J Mol Biol 89: 755–758, 1974.
Zingsheim H, Herzog W, Weber K: Differences in surface morphology of microtubules reconstituted from pure brain tubulin using two different microtubule–associated probes: the high molecular weight MAP 2 proteins and tau proteins. Eur J of Cell Biol 19: 175–183, 1979.
Luduena R, Fellous A, Francon J, Nunez J, McManus L: A hypothesis on the role of tau and high molecular weight protein (MAP 2) in microtubule assembly. J Cell Biol 87: 244a, 1980.
Oosawa F, Kasai M: Theory of linear and helical aggregations of macromolecules. J Mol Biol 4: 10–21, 1962.
Johnson K, Borisy G: The equilibrium assembly in vitro. In: Molecules and cell movement, Inoue S, Stephens R (eds), Raven Press, 1975, p 119–139.
Sternlicht H, Ringel I, Szasz J: The copolymerization of tubulin and tubulin cochicine complex in the absence and presence of associated proteins. J Biol Chem 255: 9138–9148, 1980.
Lee J, Field D, Lee L: Effects of nocodazole on structures of calf brain tubulin. Biochemistry 19: 6209–6215, 1980.
Schiff P, Fant J, Horwitz S: Promotion of microtubule assembly in vitro by taxol. Nature 277: 665–667, 1979.
Olmsted J, Marcum J, Johnson K, Allen A, Borisy G: Microtubule assembly: some possible regulatory mechanisms. J Supramol Struct 2: 429–450, 1974.
Kirschner M, Williams R, Weingarten M, Gerhart J: Microtubules from mammalian brain: some properties of their depolymerization products and a proposed mechanism for assembly and disassembly. Proc Natl Acad Sci USA 71: 1159–1163, 1974.
Lee J, Timasheff S: The reconstitution of microtubules from purified calf brain tubulin. Biochemistry 14: 5183–5187, 1975.
Bryan J: A quantitative analysis of microtubule elongation. J Cell Biol 71: 749–767, 1976.
Scheele R, Borisy G: In vitro assembly of microtubules. In: Microtubules, Roberts K, Hyams J (eds), Academic Press, 1979, p 176–254.
Kirschner M, Williams R: The mechanism of microtubule assembly in vitro. J Supramol Struct 2: 412–424, 1974.
Penningroth S: Colchicine binding to an oligomer of tubulin. Biochem Biophys Res Commun 92: 183–190, 1980.
Solomon F: Organizing microtubules in the cytoplasm. Cell 22: 331–332, 1980.
Osborn M, Weber K: The display of microtubules in transformed cells. Cell 12: 561–571, 1977.
Spiegelman B, Lopata M, Kirschner M: Multiple sites for the initiation of microtubule assembly in mammalian cells. Cell 16: 239–252, 1979.
Brinkley B, Fuller G, Highfield D: Studies of microtubules in dividing and non-dividing mammalian cells using antibody to 6S bovine brain tubulin. In: Microtubules and microtubule inhibitors, Borger SM, de Branbander M (eds), North Holland Publishers, 1975, p 297–312.
Osborn M, Weber K: Cytoplasmic microtubules in tissue culture cells appear to grow from an organizing structure towards the plasma membrane. Proc Natl Acad Sci USA 73:867– 871, 1976.
Haimo L, Telzer B, Rosenbaum J: Dynein bind to and crossbridges cytoplasmic microtubules. Proc Natl Acad Sci USA 76: 5759–5763, 1979.
Margolis R, Wilson L: Opposite end assembly and disassembly of microtubules at steady state in vitro. Cell 13: 1–8, 1978.
Bergen L, Borisy G: Head–to–tail polymerization of microtubules in vitro. Electron microscope analysis of seeded assembly. J Cell Biol 84: 141–150, 1980.
Brinkley B, Fuller G, Highfield D: Cytoplasmic microtubules in normal and transformed cells in culture. Analysis by tubulin antibody immunofluorescence. Proc Natl Acad Sci USA 72: 4981–4985, 1975.
Porter K, Puck T, Hsie W, Kelley D: An electron microscope study of the effects of dibutyryl cyclic AMP on Chinese hamster ovary cells. Cell 2: 145–162, 1974.
Berlin R, Regula C, Pfeiffer J: Microtubule assembly and disassembly at alkaline pH. In: Microtubules and microtubule inhibitors, de Branbander M, De Mey J (eds), Elsevier Press, 1980, p 145–160.
Silver R, Cole D: Isolation of mitotic apparatus containing vesicles with calcium sequestering activity. Cell 19: 505–516, 1980.
Harris P, Osborn M, Weber K: Distribution of tubulin–containing structures in the egg of the sea urchin from fertilization through first cleavage. J Cell Biol 84: 668–679, 1980.
Roobol A, Gull K, Pogson C: Evidence that griseofulvin binds to a microtubule associated protein. FEBS Lett 75: 149–153, 1977.
Gerwick W, Fenical W, Engen D, Clardy J: Isolation and structure of spatol, a potent inhibitor of cell replication from the brown seaweed spatoglossum schmittii. J Am Chem Soc 102: 7991–7993, 1980.
Jacobs R, White S, Wilson L: Selective compounds derived from marine organisms: effects on cell division in fertilized sea urchin eggs. Fed Proc 40: 26–29, 1981.
Olmsted J, Borisy G: Characterization of microtubule assembly in porcine brain extracts by viscometry. Biochemistry 12: 4282–4289, 1973.
Barnes L, Roberson G, Williams R: Binding of colchicine and colchicine analogs to tubulin. Model evidence for two binding sites. Fed Proc 39: 2162a, 1980.
Ringel I, Sternlicht H: Unpublished work.
Wilson L: Properties of colchicine binding protein from chick embryo brain. Interactions with vinca alkaloids and podophyllotoxin. Biochemistry 9: 4999–5007, 1970.
McClure W, Paulson J: The interaction of colchicine and some related alkaloids with rat brain tubulin. Mol Pharmacol 13: 560–575, 1977.
Wilson L, Friedkin M: The biochemical events of mitosis. II. The in vivo and in vitro binding of colchicine in grasshopper embryos and its possible relation to inhibition of mitosis. Biochemistry 6: 3126–2135, 1967.
Garland D: Kinetics and mechanism of colchicine binding to tubulin: evidence for ligand-induced conformational change. Biochemistry 17: 4266–4272, 1978.
Luduena R, Roach M, Garrison P: Effect of drugs on the alkylation of tubulin. J Cell Biol 75: 272a, 1977.
Morgan J, Luduena R, Spooner B: Tubulin conformation changes induced by anti-mitotic drug binding. J Cell Biol 79: 292a, 1978.
Banerjee A, Bhattacharyya B: Colcemid and colchicine binding to tubulin. FEBS Lett 99: 333–336, 1979.
Bhattacharyya B, Wolff J: Promotion of fluorescence upon binding of colchicine to tubulin. Proc Natl Acad Sci USA 71: 2627–2631, 1974.
Dietrich H, Williams R, Wilson L, Puett D: Changes in the circular dichroic spectrum of colchicine associated with tubulin binding. In: Programme abstracts, 2nd international symposium of microtubules and microtubule inhibitors, Beerse (Belgium), p 45, 1980.
David-Pfeuty T, Simon C, Panataloni D: Effect of antimitotic drugs on tubulin GTPase activity and self-assembly. J Biol Chem 254: 11696–11702, 1979.
Sternlicht H, Ringel I: Colchicine inhibition of microtubule assembly via copolymer formation. J Biol Chem 254: 10540–10550, 1979.
Barton J: Polymerization and colchicine binding: Two independent properties of tubulin. Biochim Biophys Acta 532: 155–160, 1978.
Wiche G, Honig L, Cole R: Polymerizing ability of C6 glial cell microtubule protein decays much faster than its colchicine binding activity. Nature 269: 435–436, 1977.
Schmitt H, Atlas D: Specific affinity labelling of tubulin with bromocolchicine. J Mol Biol 102: 743–758, 1976.
Schmitt H, Kram R: Binding of antimitotic drugs around cysteine residues of tubulin. Exp Cell Res 115: 408–411, 1978.
Nishida E, Kobayashi T: Relationship between tubulin SH groups and bound nucleotides. J Biochem (Tokyo) 81: 343–347, 1977.
Sheir–Neiss G, Lai M, Morris N: Indentification of a gene for β-tubulin in Aspergillus nidulans. Cell 15: 639–647, 1978.
Cabral F, Sobel M, Gottesman M: CHO mutants resistant to griseofulvin have an altered β-tubulin. Cell 20: 29–36, 1980.
Zweig M, Chignell C: Interaction of some colchicine analogs, vinblastine and podophyllotoxin with rat brain microtubule protein. Biochem Pharmacol 22: 2141–2150, 1973.
Fitzgerald T: Molecular features of colchicine associated with antimitotic activity and inhibition of tubulin polymerization. Biochem Pharmacol 25: 1383–1387, 1976.
Lettre H, Donges K, Barthold H, Fitzgerald T: Synthese neuer colchicine-derivate mit hoher antimitotischer Wirksamkeit. Liebigs Ann 758: 185–189, 1972.
Marthe G, Schwarzenberg L, Pouillart P. Oldham R, Weiner R, Jasmin C, Rosenfeld C, Hayat M, Misset J, Musset M, Schneider M, Amiel J, De Vassal F: Two epipodophyllo-toxin derivatives, VP 16213 and VM 26 in the treatment of leukemias, hematosarcomas, and lymphomas. Cancer 34: 985–992, 1974.
Loike J, Brewer C, Sternlicht H, Gensler W, Horwitz S: Structure-activity study of the inhibition of microtubule assembly in vitro by podophyllotoxin and its congeners. Cancer Res 38: 2688–2693, 1978.
Loike J, Horwitz S: Effects of VP-16-213 on the intracellular degradation of DNA in Hela Cells. Biochemistry 15: 5443–5448, 1976.
Cortese F, Bhattacharyya B, Wolff J: Podophyllotoxin as a probe for the colchicine binding site of tubulin. J Biol Chem 252: 1134–1140, 1977.
Wilson L, Anderson K, Grisham L, Chin D: Biochemical mechanisms of action of microtubule inhibitors. In: Microtubules and microtubule inhibitors, Borgers M, de Branbander M (eds), North Holland Publishers, 1975, p 103–113.
Wilson L: Microtubules as drug receptors: pharmacological properties of microtubule protein. Ann NY Acad Sci 253: 213–231, 1975.
Kelleher J: Tubulin binding affinities of podophyllotoxin and colchicine analogues. Mol Pharmacol 13: 232–241, 1977.
Brewer C, Loike J, Horwitz S, Sternlicht H, Gensler W: Coformational analysis of podo¬phyllotoxin and its congeners. Structureactivity relationship in microtubule assembly. J Med Chem 22: 215–221, 1979.
de Branbander M, Geuens G, Van de Veire R, Thone F, Aerts F, Desplenter L, DeCree J, Borgers M: The effects of R17934 (NSC 238159), a new antimicrotubular substance on the ultrastructure of neoplastic cells in vivo. Eur J Cancer 13: 511–528, 1977.
de Branbander M, Van de Veire R, Aerts F, Borgers M, Janssen P: The effects of methyl [5-(2-thienyl carbonyl)-lH-benzimidazol-2-yl carbamate, (R17934; NSC 238159], a new synthetic antitumoral drug interfering with microtubules on mammalian cells cultures in vivo. Cancer Res 36: 905–916, 1976.
Hoebeke J, Van Nigen G, de Branbander M: Interaction of oncodazole (R 17934), a new antitumoral drug, with rat brain tubulin. Biochem Biophys Res Comm 69: 319–324, 1976.
Brodie A, Potter J, Reed D: Effects of vinblastine, oncodazole, procarbazine, chlorambucil and bleomycin in vivo on colchicine binding activity of tubulin. Life Sci 24: 1547–1554, 1979.
Davidse L, Flach W: Differential binding of methyl benzimidazol-2-yl carbamate to fungal tubulin as a mechanism of resistance to this antimitotic agent in mutant strains of Aspergillus nidulans. J Cell Biol 72: 174–193, 1977.
Himes R, Kersey R, Heller-Bettinger I, Samson F: Action of the Vinca alkaloids vincristine, vinblastine, and desacetyl vinblastine amide on microtubules in vitro. Cancer Res 36: 3798–3802, 1976.
Sweeney M, Cullinan G, Poore G, Gerzon K: Experimental antitumor activity of vinblastine amides. Proc Am Assoc Cancer Res 15: 37, 1974.
Johnson I, Armstrong J, Gorman M, Burnet J: The Vinca alkaloids: a new class of oncolytic agents. Cancer Res 23: 1390–1427, 1963.
Creasey W: Modifications in biochemical pathways produced by the vinca alkaloids. Cancer Chemother Rep 52: 501–507, 1968.
Mandelbaum–Shavit F, Wolpert-Defillepes M, Johns D: Binding of Maytansine to rat brain tubulin. Biochem Biophys Res Commun 72: 47–54, 1976.
Wilson L, Anderson K, Creswell K: On the mechanism of action of vinblastine. J Cell Biol 63: 373a, 1974.
Bensch K, Malawista S: Microtubular crystals in mammalian cells. J Cell Biol 40: 95–105, 1969.
Fujiwara K, Tilney L: Substructural analysis of the microtubule and its polymorphic forms. Ann NY Acad Sci 253: 27–50, 1975.
Lee J, Harrison D, Timasheff S: Interaction of vinblastine with calf brain microtubule protein. J Biol Chem 250: 9276–9282, 1975.
Erickson H: Negatively stained vinblastine aggregates. Ann NY Acad Sci 253: 51, 1975.
Warfield R, Bouck G: Microtubule-macrotubule transitions: Intermediates after exposure to the mitotic inhibitor vinblastine. Science 186: 1219–1220, 1974.
Donoso J, Haskins K, Himes R: Effect of microtubule-associated proteins on the interaction of vincristine with microtubules and tubulin. Cancer Res 39: 1604–1610, 1979.
Haskins K, Donos J, Himes R: Spirals and paracrystals induced by vinca alkaloids: evidence that microtubule-associated proteins act as polycations. J Cell Sci 47:237–247,
Wilson L, Creswell K, Chin D: The mechanism of action of vinblastine. Binding of (acetyl-3H) vinblastine to embryonic chick brain tubulin and tubulin from sea urchin sperm tail outer doublet microtubules. Biochemistry 14: 5586–5592, 1975.
Bhattacharyya B, Wolff J: Tubulin aggregation and disaggregation: mediation by two distinct vinblastine-binding sites. Proc Natl Acad Sci USA 73: 2375–2378, 1976.
Luduena R, Ferrigini K, Roach M, Horowitz P: Contrasting effects of vinca alkaloids and ansa macrolides on the intrinsic fluorescence of tubulin. J Cell Biol 87: 243a, 1980.
Tan L, Lagnado J: Effects of indole alkaloids and related compounds on the properties of brain microtubule protein. Biochem Soc Trans 3: 121–124, 1975.
Kupchan S, Komoda Y, Court W, Thomas G, Smith R, Karim A, Gilmore C, Haltiwanger R, Bryan R: Maytansine, a novel antileukemic ansa macrolide from Maytenus ovatus. J Am Chem Soc 94: 1354–1356, 1972.
Bhattacharyya B, Wolff J: Maytansine binding to the vinblastine sites of tubulin. FEBS Lett 75: 159–162, 1977.
Remillard S, Rebhun L, Howie G, Kupchan S: Antimitotic activity of the potent tumor inhibitor Maytansine. Science 189: 1002–1005, 1975.
Luduena R, Roach M, McAda P: Correlation between the effects of drugs on microtubule assembly and on the alkylation of tubulin. J Cell Biol 79: 289a, 1978.
Kupchan S, Sneden A, Branfman A, Howie G, Rebhun L, Mclvor W, Wang R, Schnaitman T: Structural requirements for antileukemic activity among the naturally occurring and semisynthetic Maytansinoids. J Med Chem 21: 31–37, 1978.
Higashide E, Asia M, Ootsu K, Tanida S, Kozai Y, Hasegawa T, Kishi T, Sugino Y, Yoneda M: Ansamitocin, a group of novel Maytansinoid antibiotics with antitumor properties from Nocardia. Nature 270: 721–722, 1977.
Wani M, Taylor H, Wall M, Coggon P, McPhai A: Plant antitumor agents. VI. The iso¬lation and structure of taxol, a novel antileukemic and antitumor agent from taxus brevi-folia. J Am Chem Soc 93: 2325–2327, 1971.
Wall M, Wani M: Antineoplastic agents from plants. Annu Rev Pharmacol Toxicol 17: 117–132, 1977.
Schiff P, Horwitz S: Taxol stabilizes microtubules in mouse fibroblast cells. Proc Natl Acad Sci USA 77: 1561–1565, 1980.
Sandoval I, McDonald E, Jameson J, Cuatrecasas P: Role of nucleotides in tubulin polymerization: effect of guanylyl 5’-methylene diphosphonate. Proc Natl Acad Sci USA 74: 4881–4885, 1977.
Sloboda R, Malawista S, Van Blaricom, Creasey W, Rosenbaum J: Griseofulvin: in vitro microtubule assembly. J Cell Biol 70: 290a, 1976.
Wehland J, Herzog W, Weber K: Interaction of griseofulvin with microtubules, microtubule protein and tubulin. J Mol Biol 111: 329–342, 1977.
Sherline P, Schiavone K, Brocato S: Endogenous inhibitors of colchicine-tubulin binding in rat brain. Science 205: 593–595, 1979.
Lockwood A: Molecules in mammalian brain that interact with the colchicine site on tubulin. Proc Natl Acad Sci USA 76: 1184–1188, 1979.
Nunez J, Fellous A, Francon J, Lennon A: Competitive inhibition of colchicine binding to tubulin by microtubule-associated proteins. Proc Natl Acad Sci USA 76: 86–90, 1979.
Salmon E, Begg D: Functional implications of cold-stable microtubules in kinetochore fibers of insect spermatocytes during anaphase. J Cell Biol 85: 853–865, 1980.
Inoue S: The effect of colchicine on the microscopic and submicroscopic structure of the mitotic spindle. Exp Cell Res (Suppl) 2: 305–314, 1952.
Wilson L, Anderson K, Grisham L, Chin D: Biochemical mechanisms of action of microtubule inhibitors. In: Microtubules and microtubule inhibitors, Borgers M, de Brabander M (eds), North-Holland publishers, 1975, p 103–114.
Borisy G, Olmsted J, Klugman R: In vitro aggregation of cytoplasmic microtubule subunits. Proc Natl Acad Sci USA 69: 2890–2894, 1972.
Margolis R, Wilson L: Addition of colchicine–tubulin complex to microtubule ends: the mechanism of substoichiometric colchicine poisoning. Proc Natl Acad Sci USA 74:3466– 3470, 1977.
Margolis R, Wilson L, Kiefer B: Mitotic mechanism based on intrinsic microtubule behaviour. Nature 272: 450–452, 1978.
Margolis R, Rauch C, Wilson L: Mechanism of colchicinedimer addition to microtubule ends: implications for microtubule polymerization mechanism. Biochemistry 19:5550– 5557, 1980.
Sternlicht H, Ringel I, Szasz J: A kinetic model for colchicine inhibition of microtubule assembly. Biophys Disc 32: 445–448, 1980.
Sternlicht H, Ringel I, Szasz J: An analysis of the copolymerization of tubulin and tubulin. colchicine complex. Submitted for publication.
Farrell K, Wilson L: Proposed mechanism for colchicine poisoning of microtubules reassembled in vitro from Strongylocentrotus purpuratus sperm tail outer doublet tubulin. Bio-chemistry 19: 3048–3054, 1980.
Zacroff R, Weisenber R, Deery W: Equilibrium and kinetic analysis of microtubule assembly in the presence of guanosine diphosphate. J Mol Biol 139: 641–677, 1980.
Doery W, Zackroff R, Weisenberg R: Effects of microtubule associated proteins on assembly and stability of microtubule in colchicine and GDP. J Cell Biol 79: 302a, 1978.
Sternlicht H: Unpublished work.
Oakley B, Morris R: β-tubulin mutants of Aspergillus nidulans defective for microtubule assembly and function. J Cell Biol 87: 237a, 1980.
Langford G: Arrangement of subunits in microtubules with 14 protofilaments. J Cell Biol 87: 521–525, 1980.
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© 1983 Martinus Nijhoff Publishers, Boston
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Sternlicht, H. (1983). Inhibitors of Microtubule Formation. In: Humphrey, G.B., Grindey, G.B., Dehner, L.P., Acton, R.T., Pysher, T.J. (eds) Adrenal and Endocrine Tumors in Children. Cancer Treatment and Research, vol 17. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-3891-8_4
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