Rac1 and Rac3 Are Targets for Geranylgeranyltransferase I Inhibitor-Mediated Inhibition of Signaling, Transformation, and Membrane Ruffling

Cancer Research

Volumn 63, Issue 22, 2003, Pages 7959-7967

  Joyce, Patricia L ^a   Cox, Adrienne D ^a,b  

^a UNIVERSITY OF NORTH CAROLINA   (United States)

^b UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GERANYLGERANYLTRANSFERASE 1 INHIBITOR; GERANYLTRANSFERASE; RAC PROTEIN; RAC1 PROTEIN; RAC3 PROTEIN; TRANSFERASE INHIBITOR; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; CELL CYCLE; CELL FUNCTION; CONTROLLED STUDY; DRUG ACTIVITY; GENE MUTATION; GENETIC TRANSCRIPTION; MEMBRANE TRANSPORT; MOUSE; NONHUMAN; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; WILD TYPE;

ALKYL AND ARYL TRANSFERASES; ANIMALS; CELL ADHESION; CELL DIVISION; CELL MEMBRANE; CELL MOVEMENT; CELL TRANSFORMATION, NEOPLASTIC; ENZYME INHIBITORS; FARNESYLTRANSTRANSFERASE; HUMANS; JNK MITOGEN-ACTIVATED PROTEIN KINASES; MICE; MITOGEN-ACTIVATED PROTEIN KINASES; NIH 3T3 CELLS; RAC1 GTP-BINDING PROTEIN; SIGNAL TRANSDUCTION; TRANSCRIPTION FACTORS;

EID: 0344412931     PISSN: 00085472     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (46)

1. Van Aelst, L., and D'Souza-Schorey, C. Rho GTPases and signaling networks. Genes Dev., 11: 2295-2322, 1997.
2. Symons, M., and Settleman, J. Rho family GTPases: more than simple switches. Trends Cell Biol., 10: 415-419, 2000.
3. Etienne-Manneville, S., and Hall, A. Rho GTPases in cell biology. Nature (Lond.), 420: 629-635, 2002.
4. 1. Science (Wash. DC), 269: 1270-1272, 1995.
5. Nobes, C. D., and Hall, A. Rho, rac and cdc42 GTPases: regulators of actin structures, cell adhesion and motility. Biochem. Soc. Trans., 23: 456-459, 1995.
6. Nobes, C. D., and Hall, A. Rho, rac, and cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia. Cell. 81: 53-62, 1995.
7. Hill, C. S., Wynne, J., and Treisman, R. The Rho family GTPases RhoA, Rac1, and CDC42Hs regulate transcriptional activation by SRF. Cell, 81: 1159-1170, 1995.
8. Karnoub, A. E., Der, C. J., and Campbell, S. L. The insert region of Rac1 is essential for membrane ruffling but not cellular transformation. Mol. Cell. Biol., 21: 2847-2857, 2001.
9. Minden, A., Lin, A., Claret, F. X., Abo, A., and Karin, M. Selective activation of the JNK signaling cascade and c-Jun transcriptional activity by the small GTPases Rac and Cdc42Hs. Cell, 81: 1147-1157, 1995.
10. Sulciner, D. J., Irani, K., Yu, Z. X., Ferrans, V. J., Goldschmidt-Clermont, P., and Finkel, T. rac1 regulates a cytokine-stimulated, redox-dependent pathway necessary for NF-κB activation. Mol. Cell. Biol., 16: 7115-7121, 1996.
11. Westwick, J. K., Lambert, Q. T., Clark, G. J., Symons, M., Van Aelst, L., Pestell, R. G., and Der, C. J. Rac regulation of transformation, gene expression, and actin organization by multiple, PAK-independent pathways. Mol. Cell. Biol., 17: 1324-1335, 1997.
12. Page, K., Li, J., Hodge, J. A., Liu, P. T., Vanden Hoek, T. L., Becker, L. B., Pestell, R. G., Rosner, M. R., and Hershenson, M. B. Characterization of a Rac1 signaling pathway to cyclin D(I) expression in airway smooth muscle cells. J. Biol. Chem., 274: 22065-22071, 1999.
13. Khosravi-Far, R., Solski, P. A., Clark, G. J., Kinch, M. S., and Der, C. J. Activation of Rac1, RhoA, and mitogen-activated protein kinases is required for Ras transformation. Mol. Cell. Biol., 15: 6443-6453, 1995.
14. Qiu, R. G., Chen, J., Kim, D., McCormick, F., and Symons, M. An essential role for Rac in Ras transformation. Nature (Lond.), 374: 457-459, 1995.
15. Haataja, L., Groffen, J., and Heisterkamp, N. Characterization of RAC3, a novel member of the Rho family. J. Biol. Chem., 272: 20384-20388, 1997.
16. Morris, C. M., Haataja, L., McDonald, M., Gough, S., Markie, D., Groffen, J., and Heisterkamp, N. The small GTPase RAC3 gene is located within chromosome band 17q25.3 outside and telomeric of a region commonly deleted in breast and ovarian tumours. Cytogenet. Cell Genet., 89: 18-23, 2000.
17. Mira, J. P., Benard, V., Groffen, J., Sanders, L. C., and Knaus, U. G. Endogenous, hyperactive Rac3 controls proliferation of breast cancer cells by a p21-activated kinase-dependent pathway. Proc. Natl. Acad. Sci. USA, 97: 185-189, 2000.
18. Cox, A. D., and Der, C. J. Protein prenylation: more than just glue? Curr. Opin. Cell Biol., 4: 1008-1016, 1992.
19. Sebti, S. M., and Hamilton, A. D. Farnesyltransferase and geranylgeranyltransferase 1 inhibitors in cancer therapy: important mechanistic and bench to bedside issues. Expert Opin. Investig. Drugs, 9: 2767-2782, 2000.
20. Sebti, S. M., and Hamilton, A. D. Farnesyltransferase and geranylgeranyltransferase 1 inhibitors and cancer therapy: lessons from mechanism and bench-to-bedside translational studies. Oncogene, 19: 6584-6593, 2000.
21. 1 to S phase transition in mouse fibroblasts. Oncogene, 13: 1991-1999, 1996.
22. 1 and induces p21(WAF1/CIP1/SDI1) in a p53-independent manner. J. Biol. Chem., 272: 27224-27229, 1997.
23. Sun, J., Qian, Y., Hamilton, A. D., and Sebti, S. M. Both farnesyltransferase and geranylgeranyltransferase I inhibitors are required for inhibition of oncogenic K-Ras prenylation but each alone is sufficient to suppress human tumor growth in nude mouse xenografts. Oncogene, 16: 1467-1473, 1998.
24. Didsbury, J., Weber, R. F., Bokoch, G. M., Evans, T., and Snyderman, R. rac, a novel ras-related family of proteins that are botulinum toxin substrates. J. Biol. Chem., 264: 16378-16382, 1989.
25. Menard, L., Tomhave, E., Casey, P. J., Uhing, R. J., Snyderman, R., and Didsbury, J. R. Rac1, a low-molecular-mass GTP-binding-protein with high intrinsic GTPase activity and distinct biochemical properties. Eur. J. Biochem., 206: 537-546, 1992.
26. Moores, S. L., Schaber, M. D., Mosser, S. D., Rands, E., O'Hara, M. B., Garsky, V. M., Marshall, M. S., Pompliano, D. L., and Gibbs, J. B. Sequence dependence of protein isoprenylation. J. Biol. Chem., 266: 14603-14610, 1991.
27. Solski, P. A., Helms, W., Keely, P. J., Su, L., and Der, C. J. RhoA biological activity is dependent on prenylation but independent of specific isoprenoid modification. Cell Growth Differ., 13: 363-373, 2002.
28. Fiordalisi, J. J., Johnson, R. L., II, Ulku, A. S., Der, C. J., and Cox, A. D. Mammalian expression vectors for Ras family proteins: generation and use of expression constructs to analyze Ras family function. Methods Enzymol., 332: 3-36, 2001.
29. Sun, J., Blaskovich, M. A., Knowles, D., Qian, Y., Ohkanda, J., Bailey, R. D., Hamilton, A. D., and Sebti, S. M. Antitumor efficacy of a novel class of non-thiol-containing peptidomimetic inhibitors of farnesyltransferase and geranylgeranyltransferase 1: combination therapy with the cytotoxic agents cisplatin, Taxol, and gemcitabine. Cancer Res., 59: 4919-4926, 1999.
30. Cox, A. D., Solski, P. A., Jordan, J. D., and Der, C. J. Analysis of Ras protein expression in mammalian cells. Methods Enzymol., 255: 195-220, 1995.
31. Rihet, S., Vielh, P., Camonis, J., Goud, B., Chevillard, S., and de Gunzburg, J. Mutation status of genes encoding RhoA, Rac1, and Cdc42 GTPases in a panel of invasive human colorectal and breast tumors. J. Cancer Res. Clin. Oncol., 127: 733-738, 2001.
32. Schnelzer, A., Prechtel, D., Knaus, U., Dehne, K., Gerhard, M., Graeff, H., Harbeck, N., Schmitt, M., and Lengyel, E. Rac1 in human breast cancer: overexpression, mutation analysis, and characterization of a new isoform, Rac1b. Oncogene, 19: 3013-3020, 2000.
33. Bar-Sagi, D., and Hall, A. Ras and Rho GTPases: a family reunion. Cell, 103: 227-238, 2000.
34. Pruitt, K., and Der, C. J. Ras and Rho regulation of the cell cycle and oncogenesis. Cancer Lett., 171: 1-10, 2001.
35. Valencia, A., Chardin, P., Wittinghofer, A., and Sander, C. The ras protein family: evolutionary tree and role of conserved amino acids. Biochemistry, 30: 4637-4648, 1991.
36. Courjal, F., Chuchana, P., Theillet, C., and Fort, P. Structure and chromosomal assignment to 22q12 and 17qter of the ras-related Rac2 and Rac3 human genes. Genomics, 44: 242-246, 1997.
37. Walker, S. J., and Brown, H. A. Specificity of Rho insert-mediated activation of phospholipase D1. J. Biol. Chem., 277: 26260-26267, 2002.
38. Zong, H., Raman, N., Mickelson-Young, L. A., Atkinson, S. J., and Quilliam, L. A. Loop 6 of RhoA confers specificity for effector binding, stress fiber formation, and cellular transformation. J. Biol. Chem., 274: 4551-4560, 1999.
39. Thapar, R., Karnoub, A. E., and Campbell, S. L. Structural and biophysical insights into the role of the insert region in Rac1 function. Biochemistry, 41: 3875-3883, 2002.
40. Marshall, C. J. Protein prenylation: a mediator of protein-protein interactions. Science (Wash. DC), 259: 1865-1866, 1993.
41. Michaelson, D., Silletti, J., Murphy, G., D'Eustachio, P., Rush, M., and Philips, M. R. Differential localization of Rho GTPases in live cells: regulation by hypervariable regions and RhoGDI binding, J. Cell Biol., 152:111-126, 2001.
42. Cox, A. D., Hisaka, M. M., Buss, J. E., and Der, C. J. Specific isoprenoid modification is required for function of normal, but not oncogenic, Ras protein. Mol. Cell. Biol., 12: 2606-2615, 1992.
43. Cox, A. D. Farnesyltransferase inhibitors: potential role in the treatment of cancer. Drugs. 61: 723-732, 2001.
44. Cox, A. D., and Der, C. J. Farnesyltransferase inhibitors: promises and realities. Curr. Opin. Pharmacol., 2: 388-393, 2002.
45. Prendergast, G. C., and Rane, N. Farnesyltransferase inhibitors: mechanism and applications. Expert Opin. Investig. Drugs, 10: 2105-2116, 2001.
46. Adnane, J., Bizouarn, F. A., Qian, Y., Hamilton, A. D., and Sebti, S. M. p21(WAF1/CIP1) is upregulated by the geranylgeranyltransferase I inhibitor GGTI-298 through a transforming growth factor β- and Sp1-responsive element: involvement of the small GTPase rhoA. Mol. Cell. Biol., 18: 6962-6970, 1998.