Isoprenoid modifications

Protein Reviews

Volumn 13, Issue , 2011, Pages 1-37

  Nguyen, Uyen T T ^a   Goodall, Andrew ^a   Alexandrov, Kirill ^a   Abankwa, Daniel ^a  

^a NONE

Author keywords

[No Author keywords available]

Indexed keywords

DIMETHYLALLYLTRANSFERASE; GUANOSINE TRIPHOSPHATASE; ISOPRENOID; LIPID; RAB PROTEIN; RAS PROTEIN; RHO GUANINE NUCLEOTIDE BINDING PROTEIN; ZINC ION;

BINDING SITE; CELLULAR DISTRIBUTION; DRUG TARGETING; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME SPECIFICITY; ENZYME STRUCTURE; ENZYME SUBSTRATE COMPLEX; HUMAN; MEMBRANE STRUCTURE; NONHUMAN; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN FUNCTION; PROTEIN LIPID INTERACTION; PROTEIN LOCALIZATION; PROTEIN PRENYLATION; PROTEIN PROTEIN INTERACTION; PROTEIN STRUCTURE; PROTEIN TARGETING; PROTEIN TRANSPORT; REACTION ANALYSIS; REVIEW;

EID: 77958451889     PISSN: 18713025     EISSN: None     Source Type: Book Series    
DOI: 10.1007/978-1-4419-6382-6_1     Document Type: Review

References (217)

1. Abankwa, D., Gorfe, A. A., Hancock, J. F. (2007). Ras nanoclusters: molecular structure and assembly. Semin. Cell Dev. Biol. 18:599-607.
2. Abankwa, D., Gorfe, A. A., Hancock, J. F. (2008a). Mechanisms of Ras membrane organization and signalling: Ras on a rocker. Cell Cycle 7:2667-2673.
3. Abankwa, D., Hanzal-Bayer, M., Ariotti, N., et al. (2008b). A novel switch region regulates H-ras membrane orientation and signal output. EMBO J. 27:727-735.
4. Abankwa, D., and Vogel, H. (2007). A FRET map of membrane anchors suggests distinct microdomains of heterotrimeric G proteins. J. Cell Sci. 120:2953-2962.
5. Adnane, J., Seijo, E., Chen, Z., et al. (2002). RhoB, not RhoA, represses the transcription of the transforming growth factor beta type II receptor by a mechanism involving activator protein 1. J. Biol. Chem. 277:8500-8507.
6. Alexandrov, K., Simon, I., Yurchenko, V., et al. (1999). Characterization of the ternary complex between Rab7, REP-1 and Rab geranylgeranyl transferase. Eur. J. Biochem. 265:160-170.
7. Ali, B. R., Wasmeier, C., Lamoreux, L., et al. (2004). Multiple regions contribute to membrane targeting of Rab GTPases. J. Cell Sci. 117:6401-6412.
8. Alory, C., and Balch, W. E. (2000). Molecular basis for Rab prenylation. J. Cell Biol. 150:89-103.
9. Anant, J. S., and Fung, B. K. (1992). In vivo farnesylation of rat rhodopsin kinase. Biochem. Biophys. Res. Commun. 183:468-473.
10. Anderegg, R. J., Betz, R., Carr, S. A., et al. (1988). Structure of Saccharomyces cerevisiae mating hormone a-factor. Identification of S-farnesyl cysteine as a structural component. J. Biol. Chem. 263:18236-18240.
11. Andres, D. A., Milatovich, A., Ozcelik, T., et al. (1993a). cDNA cloning of the two subunits of human CAAX farnesyltransferase and chromosomal mapping of FNTA and FNTB loci and related sequences. Genomics 18:105-112.
12. Andres, D. A., Seabra, M. C., Brown, M. S., et al. (1993b). cDNA cloning of component A of Rab geranylgeranyl transferase and demonstration of its role as a Rab escort protein. Cell 73:1091-1099.
13. Apolloni, A., Prior, I. A., Lindsay, M., et al. (2000). H-ras but not K-ras traffics to the plasma membrane through the exocytic pathway. Mol. Cell Biol. 20:2475-2487.
14. Ashar, H. R., James, L., Gray, K., et al. (2000). Farnesyl transferase inhibitors block the farnesylation of CENP-E and CENP-F and alter the association of CENP-E with the microtubules. J. Biol. Chem. 275:30451-30457.
15. Barbacid, M. (1987). ras genes. Annu. Rev. Biochem. 56:779-827.
16. Baron, R., Fourcade, E., Lajoie-Mazenc, I., et al. (2000). RhoB prenylation is driven by the three carboxyl-terminal amino acids of the protein: evidenced in vivo by an anti-farnesyl cysteine antibody. Proc. Natl. Acad. Sci. U. S. A. 97:11626-11631.
17. Baron, R. A., and Seabra, M. C. (2008). Rab geranylgeranylation occurs preferentially via the preformed REP-RGGT complex and is regulated by geranylgeranyl pyrophosphate. Biochem. J. 415:67-75.
18. Basso, A. D., Kirschmeier, P., Bishop, W. R. (2006). Lipid posttranslational modifications. Farnesyl transferase inhibitors. J. Lipid Res. 47:15-31.
19. Belanis, L., Plowman, S. J., Rotblat, B., et al. (2008). Galectin-1 is a novel structural component and a major regulator of h-ras nanoclusters. Mol. Biol. Cell 19:1404-1414.
20. Berthold, J., Schenkova, K., Rivero, F. (2008). Rho GTPases of the RhoBTB subfamily and tumorigenesis. Acta Pharmacol. Sin. 29:285-295.
21. Berzat, A. C., Brady, D. C., Fiordalisi, J. J., et al. (2005). Using inhibitors of prenylation to block localization and transforming activity. Meth. Enzymol. 407:575-597.
22. Bivona, T. G., Quatela, S., Philips, M. R. (2006a). Analysis of Ras activation in living cells with GFP-RBD. Meth. Enzymol. 407:128-143.
23. Bivona, T. G., Quatela, S. E., Bodemann, B. O., et al. (2006b). PKC regulates a farnesyl-electrostatic switch on K-Ras that promotes its association with Bcl-XL on mitochondria and induces apoptosis. Mol. Cell 21:481-493.
24. Bos, J. L., Rehmann, H., Wittinghofer, A. (2007). GEFs and GAPs: critical elements in the control of small G proteins. Cell 129:865-877.
25. Bowers, K. E., and Fierke, C. A. (2004). Positively charged side chains in protein farnesyltransferase enhance catalysis by stabilizing the formation of the diphosphate leaving group. Biochemistry 43:5256-5265.
26. Buss, J. E., Quilliam, L. A., Kato, K., et al. (1991). The COOH-terminal domain of the Rap1A (Krev-1) protein is isoprenylated and supports transformation by an H-Ras:Rap1A chimeric protein. Mol. Cell Biol. 11:1523-1530.
27. Bustelo, X. R., Sauzeau, V., Berenjeno, I. M. (2007). GTP-binding proteins of the Rho/Rac family: regulation, effectors and functions in vivo. Bioessays 29:356-70.
28. Calero, M., Chen, C. Z., Zhu, W., et al. (2003). Dual prenylation is required for Rab protein localization and function. Mol. Biol. Cell 14:1852-1867.
29. Casey, P. J., and Seabra, M. C. (1996). Protein prenyltransferases. J. Biol. Chem. 271:5289-5292.
30. Caswell, P. T., Spence, H. J., Parsons, M. (2007). Rab25 associates with alpha5beta1 integrin to promote invasive migration in 3D microenvironments. Dev. Cell 13:496-510.
31. Chan, T. O., Rittenhouse, S. E., Tsichlis, P. N. (1999). AKT/PKB and other D3 phosphoinositideregulated kinases: kinase activation by phosphoinositide-dependent phosphorylation. Annu. Rev. Biochem. 68:965-1014.
32. Chang, E. C., and Philips, M. R. (2006). Spatial segregation of Ras signaling: new evidence from fission yeast. Cell Cycle 5:1936-1939.
33. Chavrier, P., Gorvel, J. P., Stelzer, E., et al. (1991). Hypervariable C-terminal domain of rab proteins acts as a targeting signal. Nature 353:769-772.
34. Chenette, E. J., Mitin, N. Y., Der, C. J. (2006). Multiple sequence elements facilitate Chp Rho GTPase subcellular location, membrane association, and transforming activity. Mol. Biol. Cell 17:3108-3121.
35. Cheng, K. W., Lahad, J. P., Kuo, W. L., et al. (2004). The RAB25 small GTPase determines aggressiveness of ovarian and breast cancers. Nat. Med. 10:1251-1256.
36. Cherfils, J., and Chardin, P. (1999). GEFs: structural basis for their activation of small GTP-binding proteins. Trends Biochem. Sci. 24:306-311.
37. Chia, W. J., and Tang, B. L. (2009). Emerging roles for Rab family GTPases in human cancer. Biochim. Biophys. Acta. 1795:110-116.
38. Chien, Y., and White, M. A. (2003). RAL GTPases are linchpin modulators of human tumour-cell proliferation and survival. EMBO Rep. 4:800-806.
39. Chook, Y. M., and Blobel, G. (2001). Karyopherins and nuclear import. Curr. Opin. Struct. Biol. 11:703-715.
40. Choy, E., Chiu, V. K., Silletti, J., et al. (1999). Endomembrane trafficking of ras: the CAAX motif targets proteins to the ER and Golgi. Cell 98:69-80.
41. Clarke, S. (1992). Protein isoprenylation and methylation at carboxyl-terminal cysteine residues. Annu. Rev. Biochem. 61:355-386.
42. Clarke, S., Vogel, J. P., Deschenes, R. J., et al. (1988). Posttranslational modification of the Ha-ras oncogene protein: evidence for a third class of protein carboxyl methyltransferases. Proc. Natl. Acad. Sci. U. S. A. 85:4643-4647.
43. Colicelli, J. (2004). Human RAS superfamily proteins and related GTPases. Sci. STKE. 250: RE13.
44. Cory, G. O., and Cullen, P. J. (2007). Membrane curvature: the power of bananas, zeppelins and boomerangs. Curr. Biol. 17: R455-R457.
45. D'Adamo, P., Menegon, A., Lo, N. C., et al. (1998). Mutations in GDI1 are responsible for X-linked non-specific mental retardation. Nat. Genet. 19:134-139
46. [see erratum in Nat. Genet. 1998, Jul; 19 (3):303].
47. Dai, Q., Choy, E., Chiu, V., et al. (1998). Mammalian prenylcysteine carboxyl methyltransferase is in the endoplasmic reticulum. J. Biol. Chem. 273:15030-15034.
48. De Smedt, F., Boom, A., Pesesse, X., et al. (1996). Post-translational modification of human brain type I inositol-1, 4, 5-trisphosphate 5-phosphatase by farnesylation. J. Biol. Chem. 271:10419-10424.
49. Denoyelle, C., Hong, L., Vannier, J. P., et al. (2003). New insights into the actions of bisphosphonate zoledronic acid in breast cancer cells by dual RhoA-dependent and-independent effects. Br. J. Cancer. 88:1631-1640.
50. Der, C. J., Krontiris, T. G., Cooper, G. M. (1982). Transforming genes of human bladder and lung carcinoma cell lines are homologous to the ras genes of Harvey and Kirsten sarcoma viruses. Proc. Natl. Acad. Sci. U. S. A. 79:3637-3640.
51. Devos, S. A., Van Den Bossche, N., De Vos, M., et al. (2003). Adverse skin reactions to anti-TNF-alpha monoclonal antibody therapy. Dermatology 206:388-390.
52. Dudler, T., and Gelb, M. H. (1996). Palmitoylation of Ha-Ras facilitates membrane binding, activation of downstream effectors, and meiotic maturation in Xenopus oocytes. J. Biol. Chem. 271:11541-11547.
53. Dunten, P., Kammlott, U., Crowther, R., et al. (1998). Protein farnesyltransferase: structure and implications for substrate binding. Biochemistry 37:7907-7912.
54. Dursina, B., Thoma, N. H., Sidorovitch, V., et al. (2002). Interaction of yeast rab geranylgeranyl transferase with its protein and lipid substrates. Biochemistry 41:6805-6816.
55. Dvorsky, R., and Ahmadian, M. R. (2004). Always look on the bright site of Rho: structural implications for a conserved intermolecular interface. EMBO Rep. 5:1130-1136.
56. Eggeling, C., Ringemann, C., Medda, R., et al. (2009). Direct observation of the nanoscale dynamics of membrane lipids in a living cell. Nature 457:1159-1162.
57. Elad-Sfadia, G., Haklai, R., Balan, E., et al. (2004). Galectin-3 augments K-Ras activation and triggers a Ras signal that attenuates ERK but not phosphoinositide 3-kinase activity. J. Biol. Chem. 279:34922-34930.
58. Etienne-Manneville, S., and Hall, A. (2002). Rho GTPases in cell biology. Nature 420:629-635.
59. Farnsworth, C. C., Seabra, M. C., Ericsson, L. H., et al. (1994). Rab geranylgeranyl transferase catalyzes the geranylgeranylation of adjacent cysteines in the small GTPases Rab1A, Rab3A, and Rab5A. Proc. Natl. Acad. Sci. U. S. A. 91:11963-11967.
60. Farnsworth, C. C., Wolda, S. L., Gelb, M. H, et al. (1989). Human lamin B contains a farnesylated cysteine residue. J. Biol. Chem. 264:20422-20429.
61. Farrell, F. X., Yamamoto, K., Lapetina, E. G. (1993). Prenyl group identification of rap2 proteins: a ras superfamily member other than ras that is farnesylated. Biochem. J. 289 (Pt 2):349-355.
62. Fivaz, M., and Meyer, T. (2005). Reversible intracellular translocation of KRas but not HRas in hippocampal neurons regulated by Ca2+/calmodulin. J. Cell Biol. 170:429-441.
63. Freeman, J. L., Abo, A., Lambeth, J. D. (1996). Rac "insert region" is a novel effector region that is implicated in the activation of NADPH oxidase, but not PAK65. J. Biol. Chem. 271:19794-19801.
64. Fukuda, M., Kanno, E., Ishibashi, K., et al. (2008). Large scale screening for novel rab effectors reveals unexpected broad Rab binding specificity. Mol. Cell. Proteomics 7:1031-1042.
65. Furfine, E. S., Leban, J. J., Landavazo, A., et al. (1995). Protein farnesyltransferase: kinetics of farnesyl pyrophosphate binding and product release. Biochemistry 34:6857-6862.
66. Gelb, M. H. 1997. Protein prenylation, etcetera: signal transduction in two dimensions. Science 275:1750-1751.
67. Gelb, M. H., Brunsveld, L., Hrycyna, C. A., et al. (2006). Therapeutic intervention based on protein prenylation and associated modifications. Nat. Chem. Biol. 2:518-528.
68. Gomes, A. Q., Ali, B. R., Ramalho, J. S., et al. (2003). Membrane targeting of Rab GTPases is influenced by the prenylation motif. Mol. Biol. Cell 14:1882-1899.
69. Goodwin, J. S., Drake, K. R., Rogers, C., et al. (2005). Depalmitoylated Ras traffics to and from the Golgi complex via a nonvesicular pathway. J. Cell Biol. 170:261-272.
70. Gorfe, A. A., Bayer, M.-H, Abankwa, D., et al. (2007). Structure and dynamics of the full-length lipid-modified H-Ras protein in a 1, 2-dimyristoylglycero-3-phosphocholine bilayer. J. Med. Chem. 50:674-684.
71. Goswami, D., Gowrishankar, K., Bilgrami, S., et al. (2008). Nanoclusters of GPI-anchored proteins are formed by cortical actin-driven activity. Cell 135:1085-1097.
72. Greenwood, J., Steinman, L., Zamvil, S. S. (2006). Statin therapy and autoimmune disease: from protein prenylation to immunomodulation. Nat. Rev. Immunol. 6:358-370.
73. Griscelli, C., Durandy, A., Guy-Grand, D., et al. (1978). A syndrome associating partial albinism and immunodeficiency. Am. J. Med. 65:691-702.
74. Grosshans, B. L., Ortiz, D., Novick, P. (2006). Rabs and their effectors: achieving specificity in membrane traffic. Proc. Natl. Acad. Sci. U. S. A. 103:11821-11827.
75. Gruenberg, J. (2003). Lipids in endocytic membrane transport and sorting. Curr. Opin. Cell Biol. 15:382-388.
76. Guo, Z., Wu, Y. W., Das, D., et al. (2008). Structures of RabGGTase-substrate/product complexes provide insights into the evolution of protein prenylation. EMBO J. 27:2444-2456.
77. Gutierrez, L., Magee, A. I., Marshall, C. J., et al. (1989). Post-translational processing of p21ras is two-step and involves carboxyl-methylation and carboxy-terminal proteolysis. EMBO J. 8:1093-1098.
78. Hancock, J. F. (2003). Ras proteins: different signals from different locations. Nat. Rev. Mol. Cell Biol. 4:373-384.
79. Hancock, J. F. (2006). Lipid rafts: contentious only from simplistic standpoints. Nat. Rev. Mol. Cell Biol. 7:456-462.
80. Hancock, J. F., Magee, A. I., Childs, J. E., et al. (1989). All ras proteins are polyisoprenylated but only some are palmitoylated. Cell 57:1167-1177.
81. Hancock, J. F., and Parton, R. G. (2005). Ras plasma membrane signalling platforms. Biochem. J. 389:1-11.
82. Hancock, J. F., Paterson, H., Marshall, C. J. (1990). A polybasic domain or palmitoylation is required in addition to the CAAX motif to localize p21ras to the plasma membrane. Cell 63:133-139.
83. Harding, A., and Hancock, J. F. (2008). Ras nanoclusters: combining digital and analog signaling. Cell Cycle 7:127-134.
84. Hartman, H. L., Bowers, K. E., Fierke, C. A. (2004). Lysine beta311 of protein geranylgeranyltransferase type I partially replaces magnesium. J. Biol. Chem. 279:30546-30553.
85. Hartman, H. L., Hicks, K. A., Fierke, C. A. (2005). Peptide specificity of protein prenyltransferases is determined mainly by reactivity rather than binding affinity. Biochemistry 44:15314-15324.
86. Harvey, J. J. (1964). An unidentified virus which causes the rapid production of tumours in mice. Nature 204:1104-1105.
87. Heasman, S. J., and Ridley, A. J. (2008). Mammalian Rho GTPases: new insights into their functions from in vivo studies. Nat. Rev. Mol. Cell. Biol. 9:690-701.
88. Heilmeyer, L. M. Jr., Serwe, M., Weber, C., et al. (1992). Farnesylcysteine, a constituent of the alpha and beta subunits of rabbit skeletal muscle phosphorylase kinase: localization by conversion to S-ethylcysteine and by tandem mass spectrometry. Proc. Natl. Acad. Sci. U. S. A. 89:9554-9558.
89. Heo, W. D., Inoue, T., Park, W. S., et al. (2006). PI (3, 4, 5) P3 and PI (4, 5) P2 lipids target proteins with polybasic clusters to the plasma membrane. Science 314:1458-1461.
90. Huang, C. C., Casey, P. J., Fierke, C. A. (1997). Evidence for a catalytic role of zinc in protein farnesyltransferase. Spectroscopy of Co2+-farnesyltransferase indicates metal coordination of the substrate thiolate. J. Biol. Chem. 272:20-23.
91. Huang, M., and Prendergast, G. C. (2006). RhoB in cancer suppression. Histol. Histopathol. 21:213-218.
92. Inglese, J., Koch, W. J., Caron, M. G., et al. (1992). Isoprenylation in regulation of signal transduction by G-protein-coupled receptor kinases. Nature 359:147-150.
93. Jacobson, K., Mouritsen, O. G., Anderson, R. G. (2007). Lipid rafts: at a crossroad between cell biology and physics. Nat. Cell Biol. 9:7-14.
94. Jaffe, A. B., and Hall, A. (2005). Rho GTPases: biochemistry and biology. Annu. Rev. Cell. Dev. Biol. 21:247-269.
95. Jefferson, A. B., Majerus, P. W. (1995). Properties of type II inositol polyphosphate 5-phosphatase. J. Biol. Chem. 270:9370-9377.
96. John, J., Rensland, H., Schlichting, I., et al. (1993). Kinetic and structural analysis of the Mg (2+)-binding site of the guanine nucleotide-binding protein p21H-ras. J. Biol. Chem. 268:923-929.
97. Joneson, T., and Bar-Sagi, D. (1998). A Rac1 effector site controlling mitogenesis through superoxide production. J. Biol. Chem. 273:17991-17994.
98. Karnoub, A. E., and Weinberg, R. A. (2008). Ras oncogenes: split personalities. Nat. Rev. Mol. Cell Biol. 9:517-531.
99. Karp, J. E. (2001). Farnesyl protein transferase inhibitors as targeted therapies for hematologic malignancies. Semin. Hematol. 38:16-23.
100. Khosravi-Far, R., Solski, P. A., Clark, G. J., et al. (1995). Activation of Rac1, RhoA, and mitogenactivated protein kinases is required for Ras transformation. Mol. Cell Biol. 15:6443-6453.
101. Kinsella, B. T., Erdman, R. A., Maltese, W. A. (1991). Carboxyl-terminal isoprenylation of rasrelated GTP-binding proteins encoded by rac1, rac2, and ralA. J. Biol. Chem. 266:9786-9794.
102. Kinsella, B. T., and Maltese, W. A. (1991). rab GTP-binding proteins implicated in vesicular transport are isoprenylated in vitro at cysteines within a novel carboxyl-terminal motif. J. Biol. Chem. 266:8540-8544.
103. Konstantinopoulos, P. A., Karamouzis, M. V., Papavassiliou, A. G. (2007). Post-translational modifications and regulation of the RAS superfamily of GTPases as anticancer targets. Nat. Rev. Drug Discov. 6:541-555.
104. Kontani, K., Tada, M., Ogawa, T., et al. (2002). Di-Ras, a distinct subgroup of ras family GTPases with unique biochemical properties. J. Biol. Chem. 277:41070-41078.
105. Kutzleb, C., Sanders, G., Yamamoto, R., et al. (1998). Paralemmin, a prenyl-palmitoyl-anchored phosphoprotein abundant in neurons and implicated in plasma membrane dynamics and cell process formation. J. Cell Biol. 143:795-813.
106. Lackner, M. R., Kindt, R. M., Carroll, P. M., et al. (2005). Chemical genetics identifies Rab geranylgeranyl transferase as an apoptotic target of farnesyl transferase inhibitors. Cancer Cell 7:325-336.
107. Lai, R. K., Perez-Sala, D., Canada, F. J., et al. (1990). The gamma subunit of transducin is farnesylated. Proc. Natl. Acad. Sci. U. S. A. 87:7673-7677.
108. Lane, K. T., and Beese, L. S. (2006). Thematic review series: lipid posttranslational modifications. Structural biology of protein farnesyltransferase and geranylgeranyltransferase type I. J. Lipid Res. 47:681-699.
109. Lerner, E. C., Hamilton, A. D., Sebti, S. M. (1997a). Inhibition of Ras prenylation: a signaling target for novel anti-cancer drug design. Anticancer Drug Des. 12:229-238.
110. Lerner, E. C., Zhang, T. T., Knowles, D. B., et al. (1997b). Inhibition of the prenylation of K-Ras, but not H-or N-Ras, is highly resistant to CAAX peptidomimetics and requires both a farnesyltransferase and a geranylgeranyltransferase I inhibitor in human tumor cell lines. Oncogene 15:1283-1288.
111. Leung, K. F., Baron, R., Ali, B. R., et al. (2007). Rab GTPases containing a CAAX motif are processed post-geranylgeranylation by proteolysis and methylation. J. Biol. Chem. 282:1487-1497.
112. Leung, K. F., Baron, R., Seabra, M. C. (2006). Thematic review series: lipid posttranslational modifications. Geranylgeranylation of Rab GTPases. J. Lipid Res. 47:467-475.
113. Leventis, R., and Silvius, J. R. (1998). Lipid-binding characteristics of the polybasic carboxy-terminal sequence of K-ras4B. Biochemistry 37:7640-7648.
114. Lichtenberg, D., Goni, F. M., Heerklotz, H. (2005). Detergent-resistant membranes should not be identified with membrane rafts. Trends Biochem. Sci. 30:430-436.
115. Long, S. B., Casey, P. J., Beese, L. S. (1998). Cocrystal structure of protein farnesyltransferase complexed with a farnesyl diphosphate substrate. Biochemistry 37:9612-9618.
116. Long, S. B., Casey, P. J., Beese, L. S. (2002). Reaction path of protein farnesyltransferase at atomic resolution. Nature 419:645-650.
117. Lowy, D. R., Johnson, M. R., DeClue, J. E., et al. (1993). Cell transformation by ras and regulation of its protein product. Ciba Found. Symp. 176:67-80; discussion 80-84.
118. Lutz, R. J., McLain, T. M., Sinensky, M. (1992). Feedback inhibition of polyisoprenyl pyrophosphate synthesis from mevalonate in vitro. Implications for protein prenylation. J. Biol. Chem. 267:7983-7986.
119. Macdonald, J. S., McCoy, S., Whitehead, R. P., et al. (2005). A phase II study of farnesyl transferase inhibitor R115777 in pancreatic cancer: a Southwest oncology group (SWOG 9924) study. Invest. New Drugs 23:485-487.
120. Maltese, W. A., and Sheridan, K. M. (1987). Isoprenylated proteins in cultured cells: subcellular distribution and changes related to altered morphology and growth arrest induced by mevalonate deprivation. J. Cell Physiol. 133:471-481.
121. Marrari, Y., Crouthamel, M., Irannejad, R., et al. (2007). Assembly and trafficking of heterotrimeric G proteins. Biochemistry 46:7665-7677.
122. Maurer-Stroh, S., Washietl, S., Eisenhaber, F. (2003). Protein prenyltransferases. Genome Biol. 4:212.
123. McBride, O. W., Swan, D. C., Santos, E., et al. (1982). Localization of the normal allele of T24 human bladder carcinoma oncogene to chromosome 11. Nature 300:773-774.
124. McPherson, R. A., Harding, A., Roy, S., et al. (1999). Interactions of c-Raf-1 with phosphatidylserine and 14-3-3. Oncogene 18:3862-3869.
125. Merithew, E., Hatherly, S., Dumas, J. J., et al. (2001). Structural plasticity of an invariant hydrophobic triad in the switch regions of Rab GTPases is a determinant of effector recognition. J. Biol. Chem. 276:13982-13988.
126. Michaelson, D., Silletti, J., Murphy, G., et al. (2001). Differential localization of Rho GTPases in live cells: regulation by hypervariable regions and RhoGDI binding. J. Cell Biol. 152:111-126.
127. Mitchell, D. A., Farh, L., Marshall, T. K., et al. (1994). A polybasic domain allows nonprenylated Ras proteins to function in Saccharomyces cerevisiae. J. Biol. Chem. 269:21540-21546.
128. Mor, A., and Philips, M. R. (2006). Compartmentalized Ras/MAPK signaling. Annu. Rev. Immunol. 24:771-800.
129. Nguyen, U. T., Guo, Z., Delon, C. et al. (2009). Analysis of the eukaryotic prenylome by isoprenoid affinity tagging. Nat. Chem. Biol. 5:227-235.
130. Nimmo, E. R., Sanders, P. G., Padua, R. A. et al. (1991). The MEL gene: a new member of the RAB/YPT class of RAS-related genes. Oncogene 6:1347-1351.
131. Nisimoto, Y., Freeman, J. L., Motalebi, S. A., et al. (1997). Rac binding to p67 (phox). Structural basis for interactions of the Rac1 effector region and insert region with components of the respiratory burst oxidase. J. Biol. Chem. 272:18834-18841.
132. Nomura, K., Kanemura, H., Satoh, T., et al. (2004). Identification of a novel domain of Ras and Rap1 that directs their differential subcellular localizations. J. Biol. Chem. 279:22664-226673.
133. Novick, P., and Zerial, M. (1997). The diversity of Rab proteins in vesicle transport. Curr. Opin. Struct. Cell Biol. 9:496-504.
134. Parada, L. F., Tabin, C. J., Shih, C. (1982). Human EJ bladder carcinoma oncogene is homologue of Harvey sarcoma virus ras gene. Nature 297:474-478.
135. Park, H. W., and Beese, L. S. (1997). Protein farnesyltransferase. Curr. Opin. Struct. Biol. 7:873-880.
136. Park, H. W., Boduluri, S. R., Moomaw, J. F., et al. (1997). Crystal structure of protein farnesyltransferase at 2.25 angstrom resolution. Science 275:1800-1804.
137. Paz, A., Haklai, R., Elad-Sfadia, G., et al. (2001). Galectin-1 binds oncogenic H-Ras to mediate Ras membrane anchorage and cell transformation. Oncogene 20:7486-7493.
138. Pereira-Leal, J. B., and Seabra, M. C. (2000). The mammalian Rab family of small GTPases: definition of family and subfamily sequence motifs suggests a mechanism for functional specificity in the Ras superfamily. J. Mol. Biol. 301:1077-1087.
139. Pfeffer, S. (2003). Membrane domains in the secretory and endocytic pathways. Cell 112:507-517.
140. Pfeffer, S., and Aivazian, D. (2004). Targeting Rab GTPases to distinct membrane compartments. Nat. Rev. Mol. Cell Biol. 5:886-896.
141. Pfeffer, S. R. (2001). Rab GTPases: specifying and deciphering organelle identity and function. Trends Cell Biol. 11:487-491.
142. Philips, M. R., and Cox, A. D. (2007). Geranylgeranyltransferase I as a target for anti-cancer drugs. J. Clin. Invest. 117:1223-1225.
143. Pickett, J. S., Bowers, K. E., Fierke, C. A. (2003). Mutagenesis studies of protein farnesyltransferase implicate aspartate beta 352 as a magnesium ligand. J. Biol. Chem. 278:51243-51250.
144. Plowman, S. J., Ariotti, N., Goodall, A., et al. (2008). Electrostatic interactions positively regulate K-Ras nanocluster formation and function. Mol. Cell Biol. 28:4377-4385.
145. Plowman, S. J., and Hancock, J. F. (2005). Ras signaling from plasma membrane and endomembrane microdomains. Biochim. Biophys. Acta. 1746:274-283.
146. Plowman, S. J., Muncke, C., Parton, R. G. (2005). H-ras, K-ras, and inner plasma membrane raft proteins operate in nanoclusters with differential dependence on the actin cytoskeleton. Proc. Natl. Acad. Sci. U. S. A. 102:15500-15505.
147. Pompliano, D. L., Schaber, M. D., Mosser, S. D., et al. (1993). Isoprenoid diphosphate utilization by recombinant human farnesyl-protein transferase. Interactive binding between substrates and a preferred kinetic pathway. Biochemistry 32:8341-8347.
148. Prior, I. A., and Hancock, J. F. (2001). Compartmentalization of Ras proteins. J. Cell Sci. 114:1603-1608.
149. Prior, I. A., Harding, A., Yan, J., et al. (2001). GTP-dependent segregation of H-ras from lipid rafts is required for biological activity. Nat. Cell Biol. 3:368-375.
150. Prior, I. A., Muncke, C., Parton, R. G., et al. (2003). Direct visualization of Ras proteins in spatially distinct cell surface microdomains. J. Cell Biol. 160:165-170.
151. Puccetti, L., Acampa, M., Auteri, A. (2007). Pharmacogenetics of statins therapy. Recent Patents Cardiovasc. Drug Discov. 2:228-236.
152. Pylypenko, O., Rak, A., Durek, T., et al. (2006). Structure of doubly prenylated Ypt1:GDI complex and the mechanism of GDI-mediated Rab recycling. EMBO J. 25:13-23.
153. Pylypenko, O., Rak, A., Reents, R., et al. (2003). Structure of rab escort protein-1 in complex with rab geranylgeranyltransferase. Mol. Cell 11:483-494.
154. Quatela, S. E., and Philips, M. R. (2006). Ras signaling on the Golgi. Curr. Opin. Cell Biol. 18:162-167.
155. Rak, A., Pylypenko, O., Niculae, A., et al. (2004). Structure of the Rab7:REP-1 complex: insights into the mechanism of Rab prenylation and choroideremia disease. Cell 117:749-760.
156. Reid, T. S., and Beese, L. S. (2004). Crystal structures of the anticancer clinical candidates R1 15777 (Tipifarnib) and BMS-214662 complexed with protein farnesyltransferase suggest a mechanism of FTI selectivity. Biochemistry 43:6877-6884.
157. Reid, T. S., Long, S. B., Beese, L. S. (2004). Crystallographic analysis reveals that anticancer clinical candidate L-778, 123 inhibits protein famesyltransferase and geranylgeranyltransferase-I by different binding modes. Biochemistry 43:9000-9008.
158. Reiss, Y., Brown, M. S., Goldstein, J. L. (1992). Divalent cation and prenyl pyrophosphate specificities of the protein farnesyltransferase from rat brain, a zinc metalloenzyme. J. Biol. Chem. 267:6403-6408.
159. Reiss, Y., Goldstein, J. L., Seabra, M. C., et al. (1990). Inhibition of purified p21ras farnesyl protein transferase by Cys-AAX tetrapeptides. Cell 62:81-88.
160. Reynwar, B. J., Illya, G., Harmandaris, V. A., et al. (2007). Aggregation and vesiculation of membrane proteins by curvature-mediated interactions. Nature 447:461-464.
161. Ridley, A. J. (2006). Rho GTPases and actin dynamics in membrane protrusions and vesicle trafficking. Trends Cell Biol. 16:522-529.
162. Rizzo, M. A., Kraft, C. A., Watkins, S. C., et al. (2001). Agonist-dependent traffic of raft-associated Ras and Raf-1 is required for activation of the mitogen-activated protein kinase cascade. J. Biol. Chem. 276:34928-34933.
163. Roberts, P. J., Mitin, N., Keller, P. J., et al. (2008). Rho Family GTPase modification and dependence on CAAX motif-signaled posttranslational modification. J. Biol. Chem. 283:25150-25163.
164. Rocks, O., Peyker, A., Kahms, M., et al. (2005). An acylation cycle regulates localization and activity of palmitoylated Ras isoforms. Science 307:1746-1752.
165. Rodriguez-Viciana, P., Sabatier, C., McCormick, F. (2004). Signaling specificity by Ras family GTPases is determined by the full spectrum of effectors they regulate. Mol. Cell Biol. 24:4943-4954.
166. Rolfe, B. E., Worth, N. F., World, C. J., et al. (2005). Rho and vascular disease. Atherosclerosis 183:1-16.
167. Rotblat, B., Niv, H., Andre, S., et al. (2004). Galectin-1 (L11A) predicted from a computed galectin-1 farnesyl-binding pocket selectively inhibits Ras-GTP. Cancer Res. 64:3112-3118.
168. Roth, A. F., Wan, J., Bailey, A. O., et al. (2006). Global analysis of protein palmitoylation in yeast. Cell 125:1003-1013.
169. Roy, S., McPherson, R. A., Reiss, A., et al. (1998). 14-3-3 facilitates Ras-dependent Raf-1 activation in vitro and in vivo. Mol. Cell Biol. 18:3947-3955.
170. Sakagami, Y., Isogai, A., Suzuki, A., et al. (1978). Amino acid sequence of tremerogen a-10, a peptidal hormone inducing conjugation tube formation in tremella mesenterica. Fr. Agric. Biol. Chem. 42:1301-1302.
171. Schaber, M. D., O'Hara, M. B., Garsky, V. M., et al. (1990). Polyisoprenylation of Ras in vitro by a farnesyl-protein transferase. J. Biol. Chem. 265:14701-14704.
172. Scheffzek, K., Ahmadian, M. R., Wiesmuller, L., et al. (1998). Structural analysis of the GAP-related domain from neurofibromin and its implications. EMBO J. 17:4313-4327.
173. Schmidt, R. A., Schneider, C. J., Glomset, J. A. (1984). Evidence for post-translational incorporation of a product of mevalonic acid into Swiss 3T3 cell proteins. J. Biol. Chem. 259:10175-10180.
174. Schmidt, W. K., Tam, A., Fujimura-Kamada, K., et al. (1998). Endoplasmic reticulum membrane localization of Rce1p and Ste24p, yeast proteases involved in carboxyl-terminal CAAX protein processing and amino-terminal a-factor cleavage. Proc. Natl. Acad. Sci. U. S. A. 95:11175-11180.
175. Seabra, M. C., Mules, E. H., Hume, A. N. (2002). Rab GTPases, intracellular traffic and disease. Trends Mol. Med. 8:23-30.
176. Seabra, M. C., Reiss, Y., Casey, P. J., et al. (1991). Protein farnesyltransferase and geranylgeranyltransferase share a common alpha subunit. Cell 65:429-434.
177. Sepp-Lorenzino, L., Ma, Z., Rands, E., et al. (1995). A peptidomimetic inhibitor of farnesyl protein transferase blocks the anchorage-dependent and-independent growth of human tumor cell lines. Cancer Res. 55:5302-5309.
178. Shalom-Feuerstein, R., Plowman, S. J., Rotblat, B., et al. (2008). K-ras nanoclustering is subverted by overexpression of the scaffold protein galectin-3. Cancer Res. 68:6608-6616.
179. Shen, F., and Seabra, M. C. (1996). Mechanism of digeranylgeranylation of Rab proteins. Formation of a complex between monogeranylgeranyl-Rab and Rab escort protein. J. Biol. Chem. 271:3692-3698.
180. Shilo, B. Z., and Weinberg, R. A. (1981). Unique transforming gene in carcinogen-transformed mouse cells. Nature 289:607-609.
181. Simons, K., and Ikonen, E. (1997). Functional rafts in cell membranes. Nature 387:569-572.
182. Simons, K., and Toomre, D. (2000). Lipid rafts and signal transduction. Nat. Rev. Mol. Cell Biol. 1:31-39.
183. Simons, K., and van Meer, G. (1988). Lipid sorting in epithelial cells. Biochemistry 27:6197-6202.
184. Sprang, S. R. (1997). G proteins, effectors and GAPs: structure and mechanism. Curr. Opin. Struct. Biol. 7:849-856.
185. Stein, M. P., Dong, J., Wandinger-Ness, A. (2003). Rab proteins and endocytic trafficking: potential targets for therapeutic intervention. Adv. Drug Deliv. Rev. 55:1421-1437.
186. Stenmark, H., and Olkkonen, V. M. (2001). The Rab GTPase family. Genome Biol. 2: REVIEWS3007.
187. Stirtan, W. G., and Poulter, C. D. (1997). Yeast protein geranylgeranyltransferase type-I: steadystate kinetics and substrate binding. Biochemistry 36:4552-4557.
188. Strickland, C. L., Windsor, W. T., Syto, R., et al. (1998). Crystal structure of farnesyl protein transferase complexed with a CaaX peptide and farnesyl diphosphate analogue. Biochemistry 37:16601-16611.
189. Swarthout, J. T., Lobo, S., Farh, L., et al. (2005). DHHC9 and GCP16 constitute a human protein fatty acyltransferase with specificity for H-and N-Ras. J. Biol. Chem. 280:31141-31148.
190. Takai, Y., Sasaki, T., Matozaki, T. (2001). Small GTP-binding proteins. Physiol. Rev. 81:153-208.
191. Tamanoi, F., Gau, C. L., Jiang, C. H., et al. (2001). Protein farnesylation in mammalian cells: effects of farnesyltransferase inhibitors on cancer cells. Cell. Mol. Life Sci. 58:1636-1649.
192. Taylor, J. S., Reid, T. S., Terry, K. L., et al. (2003). Structure of mammalian protein geranylgeranyltransferase type-I. EMBO J. 22:5963-5974.
193. Thoma, N. H., Iakovenko, A., Kalinin, A., et al. (2001). Allosteric regulation of substrate binding and product release in geranylgeranyltransferase type II. Biochemistry 40:268-274.
194. Tian, T., Harding, A., Inder, K., et al. (2007). Plasma membrane nanoswitches generate highfidelity Ras signal transduction. Nat. Cell Biol. 9:905-914.
195. Tobin, D. A., Pickett, J. S., Hartman, H. L., et al. (2003). Structural characterization of the zinc site in protein farnesyltransferase. J. Am. Chem. Soc. 125:9962-9969.
196. Troutman, J. M., Andres, D. A., Spielmann, H. P. (2007). Protein farnesyl transferase target selectivity is dependent upon peptide stimulated product release. Biochemistry 46:11299-11309.
197. Tsuchiya, E., Fukui, S., Kamiya, Y., et al. (1978). Requirements of chemical structure of hormonal activity of lipopeptidyl factors inducing sexual differentiation in vegetative cells of heterobasidiomycetous yeasts. Biochem. Biophys. Res. Commun. 85:459-463.
198. Turek-Etienne, T. C., Strickland, C. L., Distefano, M. D. (2003). Biochemical and structural studies with prenyl diphosphate analogues provide insights into isoprenoid recognition by protein farnesyl transferase. Biochemistry 42:3716-3724.
199. van den Hurk, J. A., Hendriks, W., van de Pol, D. J., et al. (1997). Mouse choroideremia gene mutation causes photoreceptor cell degeneration and is not transmitted through the female germline. Hum. Mol. Genet. 6:851-858.
200. van Meer, G., and Simons, K. (1988). Lipid polarity and sorting in epithelial cells. J. Cell Biochem. 36:51-58.
201. van Slegtenhorst, M., de Hoogt, R., Hermans, C., et al. (1997). Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34. Science 277:805-808.
202. Vega, F. M., and Ridley, A. J. (2008). Rho GTPases in cancer cell biology. FEBS Lett. 582:2093-2101.
203. Vetter, I. R., and Wittinghofer, A. (2001). The guanine nucleotide-binding switch in three dimensions. Science 294:1299-1304.
204. Wennerberg, K., Rossman, K. L., Der, C. J. (2005). The Ras superfamily at a glance. J. Cell Sci. 118:843-846.
205. Williams, C. L. (2003). The polybasic region of Ras and Rho family small GTPases: a regulator of protein interactions and membrane association and a site of nuclear localization signal sequences. Cell. Signal. 15:1071-1080.
206. Wilson, A. L., Erdman, R. A., Castellano, F., et al. (1998). Prenylation of Rab8 GTPase by type I and type II geranylgeranyl transferases. Biochem. J. 333:497-504.
207. Wu, M., Wu, Z. F., Kumar-Sinha, C., et al. (2004). RhoC induces differential expression of genes involved in invasion and metastasis in MCF10A breast cells. Breast Cancer Res. Treat. 84:3-12.
208. Wu, W. J., Leonard, D. A., A'Cerione, R., et al. (1997). Interaction between Cdc42Hs and RhoGDI is mediated through the Rho insert region. J. Biol. Chem. 272:26153-26158.
209. Wu, Y. W., Goody, R. S., Abagyan, R., et al. (2009). Structure of the disordered C-terminus of Rab7 GTPase induced by binding to the Rab geranylgeranyl transferase catalytic complex reveals the mechanism of Rab prenylation. J. Biol. Chem., 284:13185-13192.
210. Xiang, X., Zang, M., Waelde, C. A., et al. (2002). Phosphorylation of 338SSYY341 regulates specific interaction between Raf-1 and MEK1. J. Biol. Chem. 277:44996-45003.
211. Yamane, H. K., Farnsworth, C. C., Xie, H. Y., et al. (1991). Membrane-binding domain of the small G protein G25K contains an S-(all-trans-geranylgeranyl) cysteine methyl ester at its carboxyl terminus. Proc. Natl. Acad. Sci. U. S. A. 88:286-290.
212. Yeung, T., Terebiznik, M., Yu, L., et al. (2006). Receptor activation alters inner surface potential during phagocytosis. Science 313:347-351.
213. Yokoyama, K., McGeady, P., Gelb, M. H. (1995). Mammalian protein geranylgeranyltransferase-I: substrate specificity, kinetic mechanism, metal requirements, and affinity labeling. Biochemistry 34:1344-1354.
214. Zerial, M., and McBride, H. (2001). Rab proteins as membrane organizers. Nat. Rev. Mol. Cell Biol. 2:107-117.
215. Zhang, F. L., Moomaw, J. F., Casey, P. J. (1994). Properties and kinetic mechanism of recombinant mammalian protein geranylgeranyltransferase type I. J. Biol. Chem. 269:23465-23470.
216. Zhang, Y. W., Li, X. Y., Koyama, T. (2000). Chain length determination of prenyltransferases: both heteromeric subunits of medium-chain (E)-prenyl diphosphate synthase are involved in the product chain length determination. Biochemistry 39:12717-12722.
217. Zong, H., Raman, N., Mickelson-Young, L. A., et al. (1999). Loop 6 of RhoA confers specificity for effector binding, stress fiber formation, and cellular transformation. J. Biol. Chem. 274:4551-4560.