Targeting Rho GTPases by peptidic structures

Current Pharmaceutical Design

Volumn 15, Issue 21, 2009, Pages 2481-2487

  Marchioni, Filippo ^a   Zheng, Yi ^a  

^a UNIVERSITY OF CINCINNATI   (United States)

Author keywords

Cancer; Peptide inhibitors; Rho GTPases; Signaling; Targeting; Therapeutics

Indexed keywords

4 AMINO 6 [2 [[4 (DIETHYLAMINO) 1 METHYLBUTYL]AMINO] 6 METHYL 4 PYRIMIDINYL] 2 METHYLQUINOLINE; EHT 1864; GUANOSINE TRIPHOSPHATASE ACTIVATING PROTEIN; PROTEINASE INHIBITOR; RAS PROTEIN; REACTIVE OXYGEN METABOLITE; RHO GUANINE NUCLEOTIDE BINDING PROTEIN; UNCLASSIFIED DRUG;

ACTIN POLYMERIZATION; ACUTE GRANULOCYTIC LEUKEMIA; ALZHEIMER DISEASE; ANTINEOPLASTIC ACTIVITY; CARBOXY TERMINAL SEQUENCE; CARDIOVASCULAR DISEASE; CELL GROWTH; CELL MEMBRANE; CELL MIGRATION; CELL PROLIFERATION; CYTOSKELETON; DEPOLYMERIZATION; DOWN REGULATION; DRUG DESIGN; ENZYME INHIBITION; GENE ACTIVATION; GENE OVEREXPRESSION; GENETIC TRANSCRIPTION; HUMAN; MUTATIONAL ANALYSIS; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROTEIN ASSEMBLY; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; PROTEIN STRUCTURE; PROTEIN TARGETING; REVIEW; SIGNAL TRANSDUCTION; TUMOR XENOGRAFT; UPREGULATION;

ANIMALS; DRUG DESIGN; ENZYME INHIBITORS; HUMANS; MOLECULAR MIMICRY; MOLECULAR STRUCTURE; PEPTIDES; RHO GTP-BINDING PROTEINS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 69249122079     PISSN: 13816128     EISSN: None     Source Type: Journal    
DOI: 10.2174/138161209788682334     Document Type: Review

References (64)

1. Hall A. Rho GTPases and the actin cytoskeleton. Science 1998; 279: 509-14.
2. Schwartz M. Rho signalling at a glance. J Cell Sci 2004; 117: 5457-8
3. Villalonga P, Ridley AJ. Rho GTPases and cell cycle control. Growth Factors 2006; 24: 159-64.
4. Hu E. Recent patents on Rho signaling pathway as therapeutic target for cardiovascular diseases. Recent Patents Cardiovasc Drug Discov 2006; 1: 249-63.
5. Rao VP, Epstein DL. Rho GTPase/Rho kinase inhibition as a novel target for the treatment of glaucoma. BioDrugs 2007; 21: 167-77.
6. Sun D, Xu D, Zhang B. Rac signaling in tumorigenesis and as target for anticancer drug development. Drug Resist Updat 2006; 9: 274-87.
7. Cai H, Griendling KK, Harrison DG. The vascular NAD(P)H oxidases as therapeutic targets in cardiovascular diseases. Trends Pharmacol Sci 2003; 24: 471-8.
8. Zhao D, Pothoulakis C. Rho GTPases as therapeutic targets for the treatment of inflammatory diseases. Expert Opin Ther Targets 2003; 7: 583-92.
9. Schmidt A, Hall A. Guanine nucleotide exchange factors for Rho GTPases: turning on the switch. Genes Dev 2002; 16: 1587-609.
10. Karnoub A E, Symons M, Campbell SL, Der CJ. Molecular basis for Rho GTPase signaling specificity. Breast Cancer Res Treat 2004; 84: 61-71.
11. Futaki S, Goto S, Sugiura Y. Membrane permeability commonly shared among arginine-rich peptides. J Mol Recognit 2003; 16: 260-4.
12. Kinyanjui MW, Fixman ED. Cell-penetrating peptides and proteins: New inhibitors of allergic airways disease. Can J Physiol Pharmacol 2008; 86: 1-7.
13. Prive GG, Melnick A. Specific peptides for the therapeutic targeting of oncogenes. Curr Opin Genet Dev 2006; 16: 71-7.
14. Shi J, Ross CR, Leto TL, Blecha F. PR-39, a proline-rich antibacterial peptide that inhibits phagocyte NADPH oxidase activity by binding to Src homology 3 domains of p47 phox. Proc Natl Acad Sci USA 1996; 93: 6014-8.
15. Lopes NH, Vasudevan SS, Gregg D, Selvakumar B, Pagano PJ, Kovacic H, et al. Rac-dependent monocyte chemoattractant protein-1 production is induced by nutrient deprivation. Circ Res 2002; 91: 798-805.
16. Malliri A, Collard JG. Role of Rho-family proteins in cell adhesion and cancer. Curr Opin Cell Biol 2003; 15: 583-9.
17. Malliri A, van der Kammen RA, Clark K, van der Valk M, Michiels F, Collard J G. Mice deficient in the Rac activator Tiam1 are resistant to Ras-induced skin tumours. Nature 2002; 417: 867-71.
18. Mareel M, Leroy A. Clinical, cellular, and molecular aspects of cancer invasion. Physiol Rev 2003; 83: 337-76.
19. Qiu RG, Chen J, Kirn D, McCormick F, Symons M. An essential role for Rac in Ras transformation. Nature 1995; 374: 457-9.
20. Lozano E, Betson M, Braga VM. Tumor progression: Small GTPases and loss of cell-cell adhesion. Bioessays 2003; 25: 452-63.
21. Sahai E, Marshall CJ. RHO-GTPases and cancer. Nat Rev Cancer 2002; 2: 133-42.
22. Nur EK M S, Kamal JM, Qureshi MM, Maruta H. The CDC42-specific inhibitor derived from ACK-1 blocks v-Ha-Ras-induced transformation. Oncogene 1999; 18: 7787-93.
23. Qiu R G, Abo A, McCormick F, Symons M. Cdc42 regulates anchorage-independent growth and is necessary for Ras transformation. Mol Cell Biol 1997; 17: 3449-58.
24. Maruta H, He H, Tikoo A, Nur-e-Kamal M. Cytoskeletal tumor suppressors that block oncogenic RAS signaling. Ann NY Acad Sci 1999; 886: 48-57
25. Maruta H, Nheu TV, He H, Hirokawa Y. Rho family-associated kinases PAK1 and rock. Prog Cell Cycle Res 2003; 5: 203-10.
26. Shin EY, Shin KS, Lee CS, Woo KN, Quan SH, Soung NK, et al. Phosphorylation of p85 beta PIX, a Rac/Cdc42-specific guanine nucleotide exchange factor, via the Ras/ERK/PAK2 pathway is required for basic fibroblast growth factor-induced neurite outgrowth. J Biol Chem 2002; 277: 44417-30.
27. Missy K, Hu B, Schilling K, Harenberg A, Sakk V, Kuchenbecker K, et al. AlphaPIX Rho GTPase guanine nucleotide exchange factor regulates lymphocyte functions and antigen receptor signaling. Mol Cell Biol 2008; 28: 3776-89.
28. Gao Y, Xing J, Streuli M, Leto TL, Zheng Y. Trp(56) of rac1 specifies interaction with a subset of guanine nucleotide exchange factors. J Biol Chem 2001; 276: 47530-41.
29. Moon SY, Zheng Y. Rho GTPase-activating proteins in cell regulation. Trends Cell Biol 2003; 13: 13-22.
30. Yuan BZ, Miller MJ, Keck CL, Zimonjic DB, Thorgeirsson SS, Popescu NC. Cloning, characterization, and chromosomal localization of a gene frequently deleted in human liver cancer (DLC-1) homologous to rat RhoGAP. Cancer Res 1998; 58: 2196-9.
31. Wang DZ, Nur EK M S, Tikoo A, Montague W, Maruta H. The GTPase and Rho GAP domains of p190, a tumor suppressor protein that binds the M(r) 120,000 Ras GAP, independently function as anti-Ras tumor suppressors. Cancer Res 1997; 57: 2478-84.
32. Wang L, Yang L, Luo Y, Zheng Y. A novel strategy for specifically down-regulating individual Rho GTPase activity in tumor cells. J Biol Chem 2003; 278: 44617-25.
33. Bateman J, Van Vactor D. The Trio family of guanine-nucleotide-exchange factors: Regulators of axon guidance. J Cell Sci 2001; 114: 1973-80
34. Bellanger JM, Astier C, Sardet C, Ohta Y, Stossel TP, Debant A. The Rac1- and RhoG-specific GEF domain of Trio targets filamin to remodel cytoskeletal actin. Nat Cell Biol 2000; 2: 888-92.
35. Debant A, Serra-Pages C, Seipel K, O'Brien S, Tang M, Park S H, et al. The multidomain protein Trio binds the LAR transmembrane tyrosine phosphatase, contains a protein kinase domain, and has separate rac-specific and rho-specific guanine nucleotide exchange factor domains. Proc Natl Acad Sci USA 1996; 93: 5466-71.
36. Colas P, Cohen B, Jessen T, Grishina I, McCoy J, Brent R. Genetic selection of peptide aptamers that recognize and inhibit cyclin-dependent kinase 2. Nature 1996; 380: 548-50.
37. Geyer C R, Brent R. Selection of genetic agents from random peptide aptamer expression libraries. Methods Enzymol 2000; 328: 171-208.
38. Schmidt S, Diriong S, Mery J, Fabbrizio E, Debant A. Identification of the first Rho-GEF inhibitor, TRIPalpha, which targets the RhoA-specific GEF domain of Trio. FEBS Lett 2002; 523: 35-42.
39. Bokoch G M. Regulation of innate immunity by Rho GTPases. Trends Cell Biol 2005; 15: 163-71.
40. Karihtala P, Soini Y. Reactive oxygen species and antioxidant mechanisms in human tissues and their relation to malignancies. APMIS 2007; 115: 81-103.
41. Poli G, Leonarduzzi G, Biasi F, Chiarpotto E. Oxidative stress and cell signalling. Curr Med Chem 2004; 11: 1163-82.
42. Valko M, Leibfritz D, Moncol J, Cronin M T, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 2007; 39: 44-84.
43. Wu W S. The signaling mechanism of ROS in tumor progression. Cancer Metastasis Rev 2006; 25: 695-705.
44. Fruehauf J P, Meyskens F L, Jr. Reactive oxygen species: A breath of life or death? Clin Cancer Res 2007; 13: 789-94.
45. Cai H, Harrison D G. Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res 2000; 87: 840-4.
46. Bokoch G M, Diebold B A. Current molecular models for NADPH oxidase regulation by Rac GTPase. Blood 2002; 100: 2692-6.
47. Guzik T J, Harrison D G. Vascular NADPH oxidases as drug targets for novel antioxidant strategies. Drug Discov Today 2006; 11: 524-33.
48. Kreck M L, Uhlinger D J, Tyagi S R, Inge K L, Lambeth J D. Participation of the small molecular weight GTP-binding protein Rac1 in cell-free activation and assembly of the respiratory burst oxidase. Inhibition by a carboxyl-terminal Rac peptide. J Biol Chem 1994; 269: 4161-8.
49. Joseph G, Pick E. "Peptide walking" is a novel method for mapping functional domains in proteins. Its application to the Rac1-dependent activation of NADPH oxidase. J Biol Chem 1995; 270: 29079-82.
50. Gorzalczany Y, Sigal N, Itan M, Lotan O, Pick E. Targeting of Rac1 to the phagocyte membrane is sufficient for the induction of NADPH oxidase assembly. J Biol Chem 2000; 275: 40073-81.
51. Kao Y Y, Gianni D, Bohl B, Taylor R M, Bokoch G M. Identification of a conserved Rac-binding site on NADPH oxidases supports a direct GTPase regulatory mechanism. J Biol Chem 2008; 283: 12736-46.
52. Huber A B, Kolodkin A L, Ginty D D, Cloutier J F. Signaling at the growth cone: Ligand-receptor complexes and the control of axon growth and guidance. Annu Rev Neurosci 2003; 26: 509-63.
53. Luo L, O'Leary D D. Axon retraction and degeneration in development and disease. Annu Rev Neurosci 2005; 28: 127-56.
54. Fukata Y, Kimura T, Kaibuchi K. Axon specification in hippocampal neurons. Neurosci Res 2002; 43: 305-15.
55. Kubo T, Hata K, Yamaguchi A, Yamashita T. Rho-ROCK inhibitors as emerging strategies to promote nerve regeneration. Curr Pharm Des 2007; 13: 2493-9.
56. Kubo T, Yamashita T. Rho-ROCK inhibitors for the treatment of CNS injury. Recent Patents CNS Drug Discov 2007; 2: 173-9.
57. Ahmed I, Calle Y, Iwashita S, Nur E K A. Role of Cdc42 in neurite outgrowth of PC12 cells and cerebellar granule neurons. Mol Cell Biochem 2006; 281: 17-25.
58. Thies E, Davenport R W. Independent roles of Rho-GTPases in growth cone and axonal behavior. J Neurobiol 2003; 54: 358-69.
59. Gao Y, Dickerson J B, Guo F, Zheng J, Zheng Y. Rational design and characterization of a Rac GTPase-specific small molecule inhibitor. Proc Natl Acad Sci USA 2004; 101: 7618-23.
60. Nassar N, Cancelas J, Zheng J, Williams D A, Zheng Y. Structure-function based design of small molecule inhibitors targeting Rho family GTPases. Curr Top Med Chem 2006; 6: 1109-16.
61. Thomas E K, Cancelas J A, Chae H D, Cox A D, Keller P J, Perrotti D, et al. Rac guanosine triphosphatases represent integrating molecular therapeutic targets for BCR-ABL-induced myeloproliferative disease. Cancer Cell 2007; 12: 467-78.
62. Cancelas J A, Lee A W, Prabhakar R, Stringer K F, Zheng Y, Williams D A. Rac GTPases differentially integrate signals regulating hematopoietic stem cell localization. Nat Med 2005; 11: 886-91.
63. Desire L, Bourdin J, Loiseau N, Peillon H, Picard V, De Oliveira C, et al. RAC1 inhibition targets amyloid precursor protein processing by gamma-secretase and decreases Abeta production in vitro and in vivo. J Biol Chem 2005; 280: 37516-25.
64. Shutes A, Onesto C, Picard V, Leblond B, Schweighoffer F, Der C J. Specificity and mechanism of action of EHT 1864, a novel small molecule inhibitor of Rac family small GTPases. J Biol Chem 2007; 282: 35666-78.