Small molecule targeting Cdc42-intersectin interaction disrupts Golgi organization and suppresses cell motility

Proceedings of the National Academy of Sciences of the United States of America

Volumn 110, Issue 4, 2013, Pages 1261-1266

  Friesland, Amy ^a   Zhao, Yaxue ^b,c   Chen, Yan Hua ^a   Wang, Lie ^b   Zhou, Huchen ^b,c   Lu, Qun ^a  

^a EAST CAROLINA UNIVERSITY   (United States)

^b SHANGHAI JIAO TONG UNIVERSITY   (China)

^c Shanghai Jiao Tong University   (China)

Author keywords

[No Author keywords available]

Indexed keywords

4 AMINO 6 [2 [[4 (DIETHYLAMINO) 1 METHYLBUTYL]AMINO] 6 METHYL 4 PYRIMIDINYL] 2 METHYLQUINOLINE; GUANINE NUCLEOTIDE EXCHANGE FACTOR; INTERSECTIN; PROTEIN CDC42; PROTEIN INHIBITOR; RHO GUANINE NUCLEOTIDE BINDING PROTEIN; UNCLASSIFIED DRUG; ZCL 278;

ANIMAL CELL; ARTICLE; BIOACCUMULATION; CANCER CELL CULTURE; CELL MOTILITY; CELL STRAIN 3T3; CELL ULTRASTRUCTURE; CELL VIABILITY; COMPUTER MODEL; CONTROLLED STUDY; DRUG BINDING SITE; DRUG PROTEIN BINDING; DRUG SPECIFICITY; DRUG TARGETING; FIBROBLAST; GOLGI COMPLEX; GROWTH CONE; HIGH THROUGHPUT SCREENING; HUMAN; HUMAN CELL; MIGRATION INHIBITION; MOLECULAR DOCKING; MOUSE; NEUROLOGIC DISEASE; NONHUMAN; PRIORITY JOURNAL; PROTEIN PROTEIN INTERACTION; SIGNAL TRANSDUCTION;

ADAPTOR PROTEINS, VESICULAR TRANSPORT; AMINO ACID SEQUENCE; ANIMALS; BINDING SITES; CDC42 GTP-BINDING PROTEIN; CELL MOVEMENT; CELL SURVIVAL; CELLS, CULTURED; DRUG EVALUATION, PRECLINICAL; GOLGI APPARATUS; HUMANS; MICE; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; NEURONS; PROTEIN INTERACTION DOMAINS AND MOTIFS; SEQUENCE HOMOLOGY, AMINO ACID; SIGNAL TRANSDUCTION; SWISS 3T3 CELLS; USER-COMPUTER INTERFACE; WOUND HEALING;

EID: 84872870355     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1116051110     Document Type: Article

References (42)

1. Johnson D-I, Pringle J-R (1990) Molecular characterization of CDC42, a Saccharomyces cerevisiae gene involved in the development of cell polarity. J Cell Biol 111(1):143-152.
2. Cerione R-A (2004) Cdc42: New roads to travel. Trends Cell Biol 14(3):127-132.
3. Stengel K, Zheng Y (2011) Cdc42 in oncogenic transformation, invasion, and tumorigenesis. Cell Signal 23(9):1415-1423.
4. Sinha S, Yang W (2008) Cellular signaling for activation of Rho GTPase Cdc42. Cell Signal 20(11):1927-1934.
5. Lu Q, Longo F-M, Zhou H, Massa S-M, Chen Y-H (2009) Signaling through Rho GTPase pathway as viable drug target. Curr Med Chem 16(11):1355-1365.
6. Ridley A-J (2006) Rho GTPases and actin dynamics in membrane protrusions and vesicle trafficking. Trends Cell Biol 16(10):522-529.
7. Ellenbroek S-I, Collard J-G (2007) Rho GTPases: Functions and association with cancer. Clin Exp Metastasis 24(8):657-672.
8. Auer M, Hausott B, Klimaschewski L (2011) Rho GTPases as regulators of morphological neuroplasticity. Ann Anat 193(4):259-266.
9. Rihet S, et al. (2001) 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(12):733-738.
10. Lin R, Cerione R-A, Manor D (1999) Specific contributions of the small GTPases Rho, Rac, and Cdc42 to Dbl transformation. J Biol Chem 274(33):23633-23641.
11. Chen L, et al. (2010) CHD1L promotes hepatocellular carcinoma progression and metastasis in mice and is associated with these processes in human patients. J Clin Invest 120(4):1178-1191.
12. Johnson E, et al. (2010) HER2/ErbB2-induced breast cancer cell migration and invasion require p120 catenin activation of Rac1 and Cdc42. J Biol Chem 285(38):29491-29501.
13. Garvalov B-K, et al. (2007) Cdc42 regulates cofilin during the establishment of neuronal polarity. J Neurosci 27(48):13117-13129.
14. Ahmad K-F, Lim W-A (2010) The minimal autoinhibited unit of the guanine nucleotide exchange factor intersectin. PLoS ONE 5(6):e11291.
15. Goreshnik I, Maly D-J (2010) A small molecule-regulated guanine nucleotide exchange factor. J Am Chem Soc 132(3):938-940.
16. Snyder J-T, et al. (2002) Structural basis for the selective activation of Rho GTPases by Dbl exchange factors. Nat Struct Biol 9(6):468-475.
17. Kozma R, Ahmed S, Best A, Lim L (1995) The Ras-related protein Cdc42Hs and bradykinin promote formation of peripheral actin microspikes and filopodia in Swiss 3T3 fibroblasts. Mol Cell Biol 15(4):1942-1952.
18. Nobes C-D, Hall A (1995) Rho, rac and cdc42 GTPases: Regulators of actin structures, cell adhesion and motility. Biochem Soc Trans 23(3):456-459.
19. Uehata M, et al. (1997) Calcium sensitization of smooth muscle mediated by a Rhoassociated protein kinase in hypertension. Nature 389(6654):990-994.
20. Suzuki Y, et al. (1999) Agonist-induced regulation of myosin phosphatase activity in human platelets through activation of Rho-kinase. Blood 93(10):3408-3417.
21. Gao Y, Dickerson J-B, Guo F, Zheng J, Zheng Y (2004) Rational design and characterization of a Rac GTPase-specific small molecule inhibitor. Proc Natl Acad Sci USA 101(20):7618-7623.
22. Kwon T, Kwon D-Y, Chun J, Kim J-H, Kang S-S (2000) Akt protein kinase inhibits Rac1- GTP binding through phosphorylation at serine 71 of Rac1. J Biol Chem 275(1): 423-428.
23. Torres E, Rosen M-K (2003) Contingent phosphorylation/dephosphorylation provides a mechanism of molecular memory in WASP. Mol Cell 11(5):1215-1227.
24. Torres E, Rosen M-K (2006) Protein-tyrosine kinase and GTPase signals cooperate to phosphorylate and activate Wiskott-Aldrich syndrome protein (WASP)/neuronal WASP. J Biol Chem 281(6):3513-3520.
25. Harris K-P, Tepass U (2010) Cdc42 and vesicle trafficking in polarized cells. Traffic 11(10):1272-1279.
26. Erickson J-W, Zhang C, Kahn R-A, Evans T, Cerione R-A (1996) Mammalian Cdc42 is a brefeldin A-sensitive component of the Golgi apparatus. J Biol Chem 271(43): 26850-26854.
27. Nakamura N, et al. (1995) Characterization of a cis-Golgi matrix protein, GM130. J Cell Biol 131(6 Pt 2):1715-1726.
28. Gupton S-L, Gertler F-B (2007) Filopodia: The fingers that do the walking. Sci STKE 2007(400):re5.
29. Nemethova M, Auinger S, Small J-V (2008) Building the actin cytoskeleton: Filopodia contribute to the construction of contractile bundles in the lamella. J Cell Biol 180(6): 1233-1244.
30. Yang L, Wang L, Zheng Y (2006) Gene targeting of Cdc42 and Cdc42GAP affirms the critical involvement of Cdc42 in filopodia induction, directed migration, and proliferation in primary mouse embryonic fibroblasts. Mol Biol Cell 17(11):4675-4685.
31. Ridley A-J, Hall A (1992) The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors. Cell 70(3): 389-399.
32. Govek E-E, Newey S-E, Van Aelst L (2005) The role of the Rho GTPases in neuronal development. Genes Dev 19(1):1-49.
33. Brown M-D, Cornejo B-J, Kuhn T-B, Bamburg J-R (2000) Cdc42 stimulates neurite outgrowth and formation of growth cone filopodia and lamellipodia. J Neurobiol 43(4):352-364.
34. Hall A (1998) Rho GTPases and the actin cytoskeleton. Science 279(5350):509-514.
35. Jaffe A-B, Hall A (2005) Rho GTPases: Biochemistry and biology. Annu Rev Cell Dev Biol 21:247-269.
36. Wennerberg K, Der C-J (2004) Rho-family GTPases: It's not only Rac and Rho (and I like it). J Cell Sci 117(Pt 8):1301-1312.
37. Fritz G, Kaina B (2006) Rho GTPases: Promising cellular targets for novel anticancer drugs. Curr Cancer Drug Targets 6(1):1-14.
38. Pelish H-E, et al. (2006) Secramine inhibits Cdc42-dependent functions in cells and Cdc42 activation in vitro. Nat Chem Biol 2(1):39-46.
39. Boettner B, Van Aelst L (2002) The role of Rho GTPases in disease development. Gene 286(2):155-174.
40. Massa S-M, Xie Y, Longo F-M (2002) Alzheimer's therapeutics: Neurotrophin small molecule mimetics. J Mol Neurosci 19(1-2):107-111.
41. Watabe-Uchida M, Govek E-E, Van Aelst L (2006) Regulators of Rho GTPases in neuronal development. J Neurosci 26(42):10633-10635.
42. Zhou H, et al. (2006) Structure-activity studies on a library of potent calix[4]arenebased PDGF antagonists that inhibit PDGF-stimulated PDGFR tyrosine phosphorylation. Org Biomol Chem 4(12):2376-2386.