K-Ras protein as a drug target

Journal of Molecular Medicine

Volumn 94, Issue 3, 2016, Pages 253-258

  McCormick, Frank ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Cancer; K Ras proteins; K Ras therapies

Indexed keywords

CALMODULIN; GUANINE NUCLEOTIDE EXCHANGE FACTOR; K RAS PROTEIN; ANTINEOPLASTIC AGENT; RAS PROTEIN;

ANGIOGENESIS; BINDING AFFINITY; BINDING SITE; CELL MEMBRANE; ENZYME ACTIVATION; GENETIC ANALYSIS; HUMAN; NEOPLASM; NONHUMAN; PROTEIN ACETYLATION; PROTEIN ANALYSIS; PROTEIN BINDING; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN INTERACTION; PROTEIN MODIFICATION; PROTEIN PHOSPHORYLATION; PROTEIN PROCESSING; PROTEIN STRUCTURE; REVIEW; SIGNAL TRANSDUCTION; UBIQUITINATION; WNT SIGNALING PATHWAY; ANIMAL; ANTAGONISTS AND INHIBITORS; CHEMISTRY; DRUG DEVELOPMENT; DRUG EFFECTS; GENETICS; METABOLISM; MOLECULAR MODEL; MOLECULARLY TARGETED THERAPY; NEOPLASMS; PROCEDURES; PROTEIN PROTEIN INTERACTION;

ANIMALS; ANTINEOPLASTIC AGENTS; DRUG DISCOVERY; HUMANS; MODELS, MOLECULAR; MOLECULAR TARGETED THERAPY; NEOPLASMS; PROTEIN INTERACTION MAPS; PROTEIN PROCESSING, POST-TRANSLATIONAL; RAS PROTEINS;

EID: 84960104882     PISSN: 09462716     EISSN: 14321440     Source Type: Journal    
DOI: 10.1007/s00109-016-1382-7     Document Type: Review

References (30)

1. Prior IA, Lewis PD, Mattos C (2012) A comprehensive survey of Ras mutations in cancer. Cancer Res 72:2457–2467
2. Rauen KA, Schoyer L, McCormick F, Lin AE, Allanson JE, Stevenson DA, Gripp KW, Neri G, Carey JC, Legius E et al (2010) Proceedings from the 2009 genetic syndromes of the Ras/MAPK pathway: from bedside to bench and back. Am J Med Genet A 152A:4–24
3. Bourne HR, Sanders DA, McCormick F (1990) The GTPase superfamily: a conserved switch for diverse cell functions. Nature 348:125–132
4. Bos JL, Rehmann H, Wittinghofer A (2007) GEFs and GAPs: critical elements in the control of small G proteins. Cell 129:865–877
5. Cherfils J, Zeghouf M (2013) Regulation of small GTPases by GEFs, GAPs, and GDIs. Physiol Rev 93:269–309
6. Stowe IB, Mercado EL, Stowe TR, Bell EL, Oses-Prieto JA, Hernandez H, Burlingame AL, McCormick F (2012) A shared molecular mechanism underlies the human rasopathies Legius syndrome and neurofibromatosis-1. Genes Dev 26:1421–1426
7. Trahey M, McCormick F (1987) A cytoplasmic protein stimulates normal N-ras p21 GTPase, but does not affect oncogenic mutants. Science 238:542–545
8. Drosten M, Dhawahir A, Sum EY, Urosevic J, Lechuga CG, Esteban LM, Castellano E, Guerra C, Santos E, Barbacid M (2010) Genetic analysis of Ras signalling pathways in cell proliferation, migration and survival. EMBO J 29:1091–1104
9. Blasco RB, Francoz S, Santamaria D, Canamero M, Dubus P, Charron J, Baccarini M, Barbacid M (2011) c-Raf, but not B-Raf, is essential for development of K-Ras oncogene-driven non-small cell lung carcinoma. Cancer Cell 19:652–663
10. Rojas AM, Fuentes G, Rausell A, Valencia A (2012) The Ras protein superfamily: evolutionary tree and role of conserved amino acids. J Cell Biol 196:189–201
11. Rodriguez-Viciana P, Warne PH, Dhand R, Vanhaesebroeck B, Gout I, Fry MJ, Waterfield MD, Downward J (1994) Phosphatidylinositol-3-OH kinase as a direct target of Ras. Nature 370:527–532
12. Castellano E, Sheridan C, Thin MZ, Nye E, Spencer-Dene B, Diefenbacher ME, Moore C, Kumar MS, Murillo MM, Gronroos E et al (2013) Requirement for interaction of PI3-kinase p110alpha with RAS in lung tumor maintenance. Cancer Cell 24:617–630
13. Gupta S, Ramjaun AR, Haiko P, Wang Y, Warne PH, Nicke B, Nye E, Stamp G, Alitalo K, Downward J (2007) Binding of Ras to phosphoinositide 3-kinase p110alpha is required for Ras-driven tumorigenesis in mice. Cell 129:957–968
14. Murillo MM, Zelenay S, Nye E, Castellano E, Lassailly F, Stamp G, Downward J (2014) RAS interaction with PI3K p110alpha is required for tumor-induced angiogenesis. J Clin Invest 124:3601–3611
15. Shieh A, Ward AF, Donlan KL, Harding-Theobald ER, Xu J, Mullighan CG, Zhang C, Chen SC, Su X, Downing JR et al (2013) Defective K-Ras oncoproteins overcome impaired effector activation to initiate leukemia in vivo. Blood 121(24):4884-4893. doi:10.1182/blood-2012-05-432252
16. Gentry LR, Martin TD, Reiner DJ, Der CJ (2014) Ral small GTPase signaling and oncogenesis: more than just 15 minutes of fame. Biochim Biophys Acta 1843:2976–2988
17. Stephen AG, Esposito D, Bagni RK, McCormick F (2014) Dragging ras back in the ring. Cancer Cell 25:272–281
18. Cox AD, Fesik SW, Kimmelman AC, Luo J, Der CJ (2014) Drugging the undruggable RAS: mission possible? Nat Rev Drug Discov 13:828–851
19. McCormick F, Wittinghofer A (1996) Interactions between Ras proteins and their effectors. Curr Opin Biotechnol 7:449–456
20. Ostrem JM, Peters U, Sos ML, Wells JA, Shokat KM (2013) K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions. Nature 503:548–551
21. Lim SM, Westover KD, Ficarro SB, Harrison RA, Choi HG, Pacold ME, Carrasco M, Hunter J, Kim ND, Xie T et al (2014) Therapeutic targeting of oncogenic K-Ras by a covalent catalytic site inhibitor. Angew Chem Int Ed Engl 53:199–204
22. Marcus K, Mattos C (2015) Direct attack on RAS: intramolecular communication and mutation-specific effects. Clin Cancer Res 21:1810–1818
23. Cox AD, Der CJ, Philips MR (2015) Targeting RAS membrane association: back to the future for anti-RAS drug discovery? Clin Cancer Res 21:1819–1827
24. Zimmermann G, Papke B, Ismail S, Vartak N, Chandra A, Hoffmann M, Hahn SA, Triola G, Wittinghofer A, Bastiaens PI et al (2013) Small molecule inhibition of the KRAS-PDEdelta interaction impairs oncogenic KRAS signalling. Nature 497:638–642
25. Yang MH, Laurent G, Bause AS, Spang R, German N, Haigis MC, Haigis KM (2013) HDAC6 and SIRT2 regulate the acetylation state and oncogenic activity of mutant K-RAS. Mol Cancer Res 11:1072–1077
26. Sasaki AT, Carracedo A, Locasale JW, Anastasiou D, Takeuchi K, Kahoud ER, Haviv S, Asara JM, Pandolfi PP, Cantley LC (2011) Ubiquitination of K-Ras enhances activation and facilitates binding to select downstream effectors. Sci Signal 4:ra13
27. Bivona TG, Quatela SE, Bodemann BO, Ahearn IM, Soskis MJ, Mor A, Miura J, Wiener HH, Wright L, Saba SG et al (2006) 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
28. Plowman SJ, Ariotti N, Goodall A, Parton RG, Hancock JF (2008) Electrostatic interactions positively regulate K-Ras nanocluster formation and function. Mol Cell Biol 28:4377–4385
29. Villalonga P, Lopez-Alcala C, Chiloeches A, Gil J, Marais R, Bachs O, Agell N (2002) Calmodulin prevents activation of Ras by PKC in 3T3 fibroblasts. J Biol Chem 277:37929–37935
30. Wang MT, Holderfield M, Galeas J, Delrosario R, To MD, Balmain A, McCormick F (2015) KRas Promotes Tumorigenicity through Suppression of Non-canonical Wnt Signaling.Cell163(5):1237-1251. doi:10.1016/j.cell.2015.10.041