A phosphoproteomic comparison of B-RAFV600E and MKK1/2 inhibitors in melanoma cells

Molecular and Cellular Proteomics

Volumn 14, Issue 6, 2015, Pages 1599-1615

  Stuart, Scott A ^a   Houel, Stephane ^a,b   Lee, Thomas ^a   Wang, Nan ^a,c   Old, William M ^a,d   Ahn, Natalie G ^a  

^a UNIVERSITY OF COLORADO   (United States)

^b Thermo Fisher Scientific   (United States)

^c ZHEJIANG UNIVERSITY   (China)

^d UNIVERSITY OF COLORADO SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

B RAF KINASE; GROWTH FACTOR; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; MITOGEN ACTIVATED PROTEIN KINASE KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE KINASE 2; SELUMETINIB; VEMURAFENIB; BENZIMIDAZOLE DERIVATIVE; INDOLE DERIVATIVE; MAP2K1 PROTEIN, HUMAN; MAP2K2 PROTEIN, HUMAN; PHOSPHOPROTEIN; PROTEIN KINASE INHIBITOR; SULFONAMIDE;

ARTICLE; CELL SPECIFICITY; CONCENTRATION RESPONSE; ENZYME INHIBITION; GENETIC TRANSCRIPTION; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HUMAN CELL; HYDROPHILIC INTERACTION CHROMATOGRAPHY; MELANOMA CELL; NUCLEAR PORE COMPLEX; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; SIGNAL TRANSDUCTION; TANDEM MASS SPECTROMETRY; WESTERN BLOTTING; ANTAGONISTS AND INHIBITORS; MELANOMA; METABOLISM; PROTEOMICS; TUMOR CELL LINE;

BENZIMIDAZOLES; CELL LINE, TUMOR; HUMANS; INDOLES; MAP KINASE KINASE 1; MAP KINASE KINASE 2; MELANOMA; PHOSPHOPROTEINS; PROTEIN KINASE INHIBITORS; PROTEOMICS; PROTO-ONCOGENE PROTEINS B-RAF; SULFONAMIDES;

EID: 84930454887     PISSN: 15359476     EISSN: 15359484     Source Type: Journal    
DOI: 10.1074/mcp.M114.047233     Document Type: Article

References (73)

1. Matallanas, D., Birtwistle, M., Romano, D., Zebisch, A., Rauch, J., von Kriegsheim, A., and Kolch, W. (2011) Raf family kinases: Old dogs have learned new tricks. Genes Cancer 2, 232-260
2. Hindley, A., and Kolch, W. (2002) Extracellular signal regulated kinase (ERK)/mitogen activated protein kinase (MAPK)-independent functions of Raf kinases. J. Cell Sci. 115, 1575-1581
3. Roskoski, R. (2012) MEK1/2 dual-specificity protein kinases: structure and regulation. Biochem. Biophys. Res. Commun. 417, 5-10
4. Yoon, S., and Seger, R. (2006) The extracellular signal-regulated kinase: multiple substrates regulate diverse cellular functions. Growth Factors 24, 21-44
5. Davies, H., Bignell, G. R., Cox, C., Stephens, P., Edkins, S., Clegg, S., Teague, J., Woffendin, H., Garnett, M. J., Bottomley, W., Davis, N., Dicks, E., Ewing, R., Floyd, Y., Gray, K., Hall, S., Hawes, R., Hughes, J., Kosmidou, V., Menzies, A., Mould, C., Parker, A., Stevens, C., Watt, S., Hooper, S., Wilson, R., Jayatilake, H., Gusterson, B. A., Cooper, C., Shipley, J., Hargrave, D., Pritchard-Jones, K., Maitland, N., Chenevix-Trench, G., Riggins, G. J., Bigner, D. D., Palmieri, G., Cossu, A., Flanagan, A., Nicholson, A., Ho, J. W. C., Leung, S. Y., Yuen, S. T., Weber, B. L., Seigler, H. F., Darrow, T. L., Paterson, H., Marais, R., Marshall, C. J., Wooster, R., Stratton, M. R., and Futreal, P. A. (2002) Mutations of the BRAF gene in human cancer. Nature 417, 949-954
6. Sullivan, R. J., Lorusso, P. M., and Flaherty, K. T. (2013) The intersection of immune-directed and molecularly targeted therapy in advanced melanoma: where we have been, are, and will be. Clin. Cancer Res. 19, 5283-5291
7. Van Raamsdonk, C. D., Bezrookove, V., Green, G., Bauer, J., Gaugler, L., O'Brien, J. M., Simpson, E. M., Barsh, G. S., and Bastian, B. C. (2009) Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi. Nature 457, 599-602
8. Van Raamsdonk, C. D., Griewank, K. G., Crosby, M. B., Garrido, M. C., Vemula, S., Wiesner, T., Obenauf, A. C., Wackernagel, W., Green, G., Bouvier, N., Sozen, M. M., Baimukanova, G., Roy, R., Heguy, A., Dolgalev, I., Khanin, R., Busam, K., Speicher, M. R., O'Brien, J., and Bastian, B. C. (2010) Mutations in GNA11 in uveal melanoma. N. Engl. J. Med. 363, 2191-2199
9. Andersen, L. B., Fountain, J. W., Gutmann, D. H., Tarlé, S. A., Glover, T. W., Dracopoli, N. C., Housman, D. E., and Collins, F. S. (1993) Mutations in the neurofibromatosis 1 gene in sporadic malignant melanoma cell lines. Nat. Genet. 3, 118-121
10. Chapman, P. B., Hauschild, A., Robert, C., Haanen, J. B., Ascierto, P., Larkin, J., Dummer, R., Garbe, C., Testori, A., Maio, M., Hogg, D., Lorigan, P., Lebbe, C., Jouary, T., Schadendorf, D., Ribas, A., O'Day, S. J., Sosman, J. a, Kirkwood, J. M., Eggermont, A. M. M., Dreno, B., Nolop, K., Li, J., Nelson, B., Hou, J., Lee, R. J., Flaherty, K. T., and McArthur, G. A. (2011) Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N. Engl. J. Med. 364, 2507-2516
11. Hauschild, A., Grob, J.-J., Demidov, L. V, Jouary, T., Gutzmer, R., Millward, M., Rutkowski, P., Blank, C. U., Miller, W. H., Kaempgen, E., Martín- Algarra, S., Karaszewska, B., Mauch, C., Chiarion-Sileni, V., Martin, A.-M., Swann, S., Haney, P., Mirakhur, B., Guckert, M. E., Goodman, V., and Chapman, P. B. (2012) Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet 380, 358-365
12. Flaherty, K. T., Robert, C., Hersey, P., Nathan, P., Garbe, C., Milhem, M., Demidov, L. V, Hassel, J. C., Rutkowski, P., Mohr, P., Dummer, R., Trefzer, U., Larkin, J. M. G., Utikal, J., Dreno, B., Nyakas, M., Middleton, M. R., Becker, J. C., Casey, M., Sherman, L. J., Wu, F. S., Ouellet, D., Martin, A.-M., Patel, K., and Schadendorf, D. (2012) Improved survival with MEK inhibition in BRAF-mutated melanoma. N. Engl. J. Med. 367, 107-114
13. Larkin, J., Ascierto, P. A., Dréno, B., Atkinson, V., Liszkay, G., Maio, M., Mandalà , M., Demidov, L., Stroyakovskiy, D., Thomas, L., Merino, L. D. L. C., Dutriaux, C., Garbe, C., Sovak, M. A., Chang, I., Choong, N., Hack, S. P., McArthur, G. A., and Ribas, A. (2014) Combined Vemurafenib and Cobimetinib in BRAF -Mutated Melanoma. N. Engl. J. Med. 371, 1867-1876
14. Carvajal, R. D., Sosman, J. A., Quevedo, J. F., Milhem, M. M., Joshua, A. M., Kudchadkar, R. R., Linette, G. P., Gajewski, T. F., Lutzky, J., Lawson, D. H., Lao, C. D., Flynn, P. J., Albertini, M. R., Sato, T., Lewis, K., Doyle, A., Ancell, K., Panageas, K. S., Bluth, M., Hedvat, C., Erinjeri, J., Ambrosini, G., Marr, B., Abramson, D. H., Dickson, M. A., Wolchok, J. D., Chapman, P. B., and Schwartz, G. K. (2014) Effect of selumetinib vs chemotherapy on progression-free survival in uveal melanoma: a randomized clinical trial. Jama 311, 2397-2405
15. Robert, C., Karaszewska, B., Schachter, J., Rutkowski, P., Mackiewicz, A., Stroiakovski, D., Lichinitser, M., Dummer, R., Grange, F., Mortier, L., Chiarion-Sileni, V., Drucis, K., Krajsova, I., Hauschild, A., Lorigan, P., Wolter, P., Long, G. V., Flaherty, K., Nathan, P., Ribas, A., Martin, A.-M., Sun, P., Crist, W., Legos, J., Rubin, S. D., Little, S. M., and Schadendorf, D. (2014) Improved Overall Survival in Melanoma with Combined Dabrafenib and Trametinib. N. Engl. J. Med.
16. Flaherty, K. T., Infante, J. R., Daud, A., Gonzalez, R., Kefford, R. F., Sosman, J., Hamid, O., Schuchter, L., Cebon, J., Ibrahim, N., Kudchadkar, R., Burris, H. A., Falchook, G., Algazi, A., Lewis, K., Long, G. V, Puzanov, I., Lebowitz, P., Singh, A., Little, S., Sun, P., Allred, A., Ouellet, D., Kim, K. B., Patel, K., and Weber, J. (2012) Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. N. Engl. J. Med. 367, 1694-1703
17. Long, G. V., Stroyakovskiy, D., Gogas, H., Levchenko, E., de Braud, F., Larkin, J., Garbe, C., Jouary, T., Hauschild, A., Grob, J. J., Sileni, V. C., Lebbe, C., Mandalà , M., Millward, M., Arance, A., Bondarenko, I., Haanen, J. B. a. G., Hansson, J., Utikal, J., Ferraresi, V., Kovalenko, N., Mohr, P., Probachai, V., Schadendorf, D., Nathan, P., Robert, C., Ribas, A., DeMarini, D. J., Irani, J. G., Casey, M., Ouellet, D., Martin, A.-M., Le, N., Patel, K., and Flaherty, K. (2014) Combined BRAF and MEK Inhibition versus BRAF Inhibition Alone in Melanoma. N. Engl. J. Med. 371, 1877-8188
18. Paraiso, K. H. T., Fedorenko, I. V, Cantini, L. P., Munko, A. C., Hall, M., Sondak, V. K., Messina, J. L., Flaherty, K. T., and Smalley, K. S. M. (2010) Recovery of phospho-ERK activity allows melanoma cells to escape from BRAF inhibitor therapy. Br. J. Cancer 102, 1724-1730
19. Bollag, G., Hirth, P., Tsai, J., Zhang, J., Ibrahim, P. N., Cho, H., Spevak, W., Zhang, C., Zhang, Y., Habets, G., Burton, E. A., Wong, B., Tsang, G., West, B. L., Powell, B., Shellooe, R., Marimuthu, A., Nguyen, H., Zhang, K. Y. J., Artis, D. R., Schlessinger, J., Su, F., Higgins, B., Iyer, R., D'Andrea, K., Koehler, A., Stumm, M., Lin, P. S., Lee, R. J., Grippo, J., Puzanov, I., Kim, K. B., Ribas, A., McArthur, G. A., Sosman, J. A., Chapman, P. B., Flaherty, K. T., Xu, X., Nathanson, K. L., and Nolop, K. (2010) Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma. Nature 467, 596-599
20. Hartsough, E., Shao, Y., and Aplin, A. E. (2014) Resistance to RAF inhibitors revisited. J. Invest. Dermatol. 134, 319-325
21. Lewis, T. S., Hunt, J. B., Aveline, L. D., Jonscher, K. R., Louie, D. F., Yeh, J. M., Nahreini, T. S., Resing, K. A., and Ahn, N. G. (2000) Identification of Novel MAP Kinase Pathway Signaling Targets by Functional Proteomics and Mass Spectrometry. Mol. Cell 6, 1343-1354
22. Kosako, H., Yamaguchi, N., Aranami, C., Ushiyama, M., Kose, S., Imamoto, N., Taniguchi, H., Nishida, E., and Hattori, S. (2009) Phosphoproteomics reveals new ERK MAP kinase targets and links ERK to nucleoporinmediated nuclear transport. Nat. Struct. Mol. Biol. 16, 1026-1035
23. Eblen, S. T., Kumar, N. V., Shah, K., Henderson, M. J., Watts, C. K. W., Shokat, K. M., and Weber, M. J. (2003) Identification of novel ERK2 substrates through use of an engineered kinase and ATP analogs. J. Biol. Chem. 278, 14926-14935
24. Carlson, S. M., Chouinard, C. R., Labadorf, A., Lam, C. J., Schmelzle, K., Fraenkel, E., and White, F. M. (2011) Large-scale discovery of ERK2 substrates identifies ERK-mediated transcriptional regulation by ETV3. Sci. Signal. 4, rs11
25. Old, W. M., Shabb, J. B., Houel, S., Wang, H., Couts, K. L., Yen, C.-Y., Litman, E. S., Croy, C. H., Meyer-Arendt, K., Miranda, J. G., Brown, R. A., Witze, E. S., Schweppe, R. E., Resing, K. A., and Ahn, N. G. (2009) Functional proteomics identifies targets of phosphorylation by B-Raf signaling in melanoma. Mol. Cell 34, 115-131
26. Pan, C., Olsen, J. V, Daub, H., and Mann, M. (2009) Global effects of kinase inhibitors on signaling networks revealed by quantitative phosphoproteomics. Mol. Cell. Proteomics 8, 2796-2808
27. Galan, J. A., Geraghty, K. M., Lavoie, G., Kanshin, E., Tcherkezian, J., Calabrese, V., Jeschke, G. R., Turk, B. E., Ballif, B. A., Blenis, J., Thibault, P., and Roux, P. P. (2014) Phosphoproteomic analysis identifies the tumor suppressor PDCD4 as a RSK substrate negatively regulated by 14-3-3. Proc. Natl. Acad. Sci. U. S. A. 111, E2918-2927
28. Courcelles, M., Frémin, C., Voisin, L., Lemieux, S., Meloche, S., and Thibault, P. (2013) Phosphoproteome dynamics reveal novel ERK1/2 MAP kinase substrates with broad spectrum of functions. Mol. Syst. Biol. 9, 669
29. Parker, R., Clifton-Bligh, R., and Molloy, M. P. (2014) Phosphoproteomics of MAPK inhibition in BRAF-mutated cells and a role for the lethal synergism of dual BRAF and CK2 inhibition. Mol. Cancer Ther. 13, 1894-1906
30. Wis̈niewski, J. R., Zougman, A., Nagaraj, N., and Mann, M. (2009) Universal sample preparation method for proteome analysis. Nat. Methods 6, 359-362
31. Cox, J., and Mann, M. (2008) MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nat. Biotechnol. 26, 1367-1372
32. Vizcaíno, J. A., Deutsch, E. W., Wang, R., Csordas, A., Reisinger, F., Ríos, D., Dianes, J. A., Sun, Z., Farrah, T., Bandeira, N., Binz, P.-A., Xenarios, I., Eisenacher, M., Mayer, G., Gatto, L., Campos, A., Chalkley, R. J., Kraus, H.-J., Albar, J. P., Martinez-Bartolomé, S., Apweiler, R., Omenn, G. S., Martens, L., Jones, A. R., and Hermjakob, H. (2014) ProteomeXchange provides globally coordinated proteomics data submission and dissemination. Nat. Biotechnol. 32, 223-226
33. Ong, S.-E., and Mann, M. (2006) A practical recipe for stable isotope labeling by amino acids in cell culture (SILAC). Nat. Protoc. 1, 2650-2660
34. Alpert, A., Mitulovi, G., and Mechtler, K. in HPLC 2008 Conference (Baltimore, MD), p Poster P-2412-W.
35. Boichenko, A. P., Govorukhina, N., van der Zee, A. G. J., and Bischoff, R. (2013) Multidimensional separation of tryptic peptides from human serum proteins using reversed-phase, strong cation exchange, weak anion exchange, and fused-core fluorinated stationary phases. J. Sep. Sci. 36, 3463-3470
36. Olsen, J. V, Blagoev, B., Gnad, F., Macek, B., Kumar, C., Mortensen, P., and Mann, M. (2006) Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 127, 635-648
37. Basbous, J., Chalbos, D., Hipskind, R., Jariel-Encontre, I., and Piechaczyk, M. (2007) Ubiquitin-independent proteasomal degradation of Fra-1 is antagonized by Erk1/2 pathway-mediated phosphorylation of a unique C-terminal destabilizer. Mol. Cell. Biol. 27, 3936-3950
38. Snel, B., Lehmann, G., Bork, P., and Huynen, M. A. (2000) STRING: a web-server to retrieve and display the repeatedly occurring neighbourhood of a gene. Nucleic Acids Res. 28, 3442-3444
39. Von Mering, C., Jensen, L. J., Kuhn, M., Chaffron, S., Doerks, T., Krüger, B., Snel, B., and Bork, P. (2007) STRING 7-recent developments in the integration and prediction of protein interactions. Nucleic Acids Res. 35, D358-362
40. Gille, H., Kortenjann, M., Thomae, O., Moomaw, C., Slaughter, C., Cobb, M. H., and Shaw, P. E. (1995) ERK phosphorylation potentiates Elk-1- mediated ternary complex formation and transactivation. EMBO J. 14, 951-962
41. Pulverer, B. J., Kyriakis, J. M., Avruch, J., Nikolakaki, E., and Woodgett, J. R. (1991) Phosphorylation of c-jun mediated by MAP kinases. Nature 353, 670-674
42. Young, M. R., Nair, R., Bucheimer, N., Tulsian, P., Brown, N., Chapp, C., Hsu, T., and Colburn, N. H. (2002) Transactivation of Fra-1 and consequent activation of AP-1 occur extracellular signal-regulated kinase dependently. Mol. Cell. Biol. 22, 587-598
43. Alvarez, E., Northwood, I. C., Gonzalez, F. A., Latour, D. A., Seth, A., Abate, C., Curran, T., and Davis, R. J. (1991) Pro-Leu-Ser/Thr-Pro is a consensus primary sequence for substrate protein phosphorylation. Characterization of the phosphorylation of c-myc and c-jun proteins by an epidermal growth factor receptor threonine 669 protein kinase. J. Biol. Chem. 266, 15277-15285
44. Mi, H., Muruganujan, A., Casagrande, J. T., and Thomas, P. D. (2013) Large-scale gene function analysis with the PANTHER classification system. Nat. Protoc. 8, 1551-66
45. Benedit, P., Paciucci, R., Thomson, T. M., Valeri, M., Nadal, M., Cà ceres, C., de Torres, I., Estivill, X., Lozano, J. J., Morote, J., and Reventós, J. (2001) PTOV1, a novel protein overexpressed in prostate cancer containing a new class of protein homology blocks. Oncogene 20, 1455-1464
46. Yoshida, H., Okada, T., Haze, K., Yanagi, H., Yura, T., Negishi, M., and Mori, K. (2000) ATF6 activated by proteolysis binds in the presence of NF-Y (CBF) directly to the cis-acting element responsible for the mammalian unfolded protein response. Mol. Cell. Biol. 20, 6755-6767
47. Massari, M. E., Jennings, P. A., and Murre, C. (1996) The AD1 transactivation domain of E2A contains a highly conserved helix which is required for its activity in both Saccharomyces cerevisiae and mammalian cells. Mol. Cell. Biol. 16, 121-129
48. Cowell, I. G., and Hurst, H. C. (1994) Transcriptional repression by the human bZIP factor E4BP4: definition of a minimal repression domain. Nucleic Acids Res. 22, 59-65
49. Sharp, T. V, Munoz, F., Bourboulia, D., Presneau, N., Darai, E., Wang, H.-W., Cannon, M., Butcher, D. N., Nicholson, A. G., Klein, G., Imreh, S., and Boshoff, C. (2004) LIM domains-containing protein 1 (LIMD1), a tumor suppressor encoded at chromosome 3p21.3, binds pRB and represses E2F-driven transcription. Proc. Natl. Acad. Sci. U. S. A. 101, 16531-16536
50. Hornbeck, P. V, Kornhauser, J. M., Tkachev, S., Zhang, B., Skrzypek, E., Murray, B., Latham, V., and Sullivan, M. (2012) PhosphoSitePlus: a comprehensive resource for investigating the structure and function of experimentally determined post-translational modifications in man and mouse. Nucleic Acids Res. 40, D261-270
51. Dougherty, M. K., Müller, J., Ritt, D. A., Zhou, M., Zhou, X. Z., Copeland, T. D., Conrads, T. P., Veenstra, T. D., Lu, K. P., and Morrison, D. K. (2005) Regulation of Raf-1 by direct feedback phosphorylation. Mol. Cell 17, 215-224
52. Tigno-Aranjuez, J. T., Asara, J. M., and Abbott, D. W. (2010) Inhibition of RIP2's tyrosine kinase activity limits NOD2-driven cytokine responses. Genes Dev. 24, 2666-2677
53. Navas, T. A., Baldwin, D. T., and Stewart, T. A. (1999) RIP2 is a Raf1- activated mitogen-activated protein kinase kinase. J. Biol. Chem. 274, 33684-33690
54. Zhao, W., Sachsenmeier, K., Zhang, L., Sult, E., Hollingsworth, R. E., and Yang, H. (2014) A New Bliss Independence Model to Analyze Drug Combination Data. J. Biomol. Screen. 19, 817-821
55. Wagle, N., Van Allen, E. M., Treacy, D. J., Frederick, D. T., Cooper, Z. A., Taylor-Weiner, A., Rosenberg, M., Goetz, E. M., Sullivan, R. J., Farlow, D. N., Friedrich, D. C., Anderka, K., Perrin, D., Johannessen, C. M., McKenna, A., Cibulskis, K., Kryukov, G., Hodis, E., Lawrence, D. P., Fisher, S., Getz, G., Gabriel, S. B., Carter, S. L., Flaherty, K. T., Wargo, J. A., and Garraway, L. A. (2014) MAP kinase pathway alterations in BRAF-mutant melanoma patients with acquired resistance to combined RAF/MEK inhibition. Cancer Discov. 4, 61-68
56. Poulikakos, P. I., Persaud, Y., Janakiraman, M., Kong, X., Ng, C., Moriceau, G., Shi, H., Atefi, M., Titz, B., Gabay, M. T., Salton, M., Dahlman, K. B., Tadi, M., Wargo, J. A., Flaherty, K. T., Kelley, M. C., Misteli, T., Chapman, P. B., Sosman, J. A., Graeber, T. G., Ribas, A., Lo, R. S., Rosen, N., and Solit, D. B. (2011) RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E). Nature 480, 387-390
57. Gan, C. S., Guo, T., Zhang, H., Lim, S. K., and Sze, S. K. (2008) A comparative study of electrostatic repulsion-hydrophilic interaction chromatography (ERLIC) versus SCX-IMAC-based methods for phosphopeptide isolation/enrichment. J. Proteome Res. 7, 4869-4877
58. Zarei, M., Sprenger, A., Metzger, F., Gretzmeier, C., and Dengjel, J. (2011) Comparison of ERLIC-TiO2, HILIC-TiO2, and SCX-TiO2 for global phosphoproteomics approaches. J. Proteome Res. 10, 3474-3483
59. Zarei, M., Sprenger, A., Gretzmeier, C., and Dengjel, J. (2012) Combinatorial use of electrostatic repulsion-hydrophilic interaction chromatography (ERLIC) and strong cation exchange (SCX) chromatography for in-depth phosphoproteome analysis. J. Proteome Res. 11, 4269-4276
60. Zarei, M., Sprenger, A., Gretzmeier, C., and Dengjel, J. (2013) Rapid combinatorial ERLIC-SCX solid-phase extraction for in-depth phosphoproteome analysis. J. Proteome Res. 12, 5989-5995
61. Fernández, S., Mosquera, J. L., Alaña, L., Sanchez-Pla, A., Morote, J., Ramón Y Cajal, S., Reventós, J., de Torres, I., and Paciucci, R. (2011) PTOV1 is overexpressed in human high-grade malignant tumors. Virchows Arch. 458, 323-330
62. Wang, S., Robertson, G. P., and Zhu, J. (2004) A novel human homologue of Drosophila polycomblike gene is up-regulated in multiple cancers. Gene 343, 69-78
63. Jiang, C. C., Chen, L. H., Gillespie, S., Wang, Y. F., Kiejda, K. A., Zhang, X. D., and Hersey, P. (2007) Inhibition of MEK sensitizes human melanoma cells to endoplasmic reticulum stress-induced apoptosis. Cancer Res. 67, 9750-9761
64. Jiang, C. C., Lucas, K., Avery-Kiejda, K. A., Wade, M., DeBock, C. E., Thorne, R. F., Allen, J., Hersey, P., and Zhang, X. D. (2008) Up-regulation of Mcl-1 is critical for survival of human melanoma cells upon endoplasmic reticulum stress. Cancer Res. 68, 6708-6717
65. Wang, Y., Vera, L., Fischer, W. H., and Montminy, M. (2009) The CREB coactivator CRTC2 links hepatic ER stress and fasting gluconeogenesis. Nature 460, 534-537
66. Hömig-Hölzel, C., van Doorn, R., Vogel, C., Germann, M., Cecchini, M. G., Verdegaal, E., and Peeper, D. S. (2011) Antagonistic TSC22D1 variants control BRAF(E600)-induced senescence. EMBO J. 30, 1753-1765
67. Johannessen, C. M., Boehm, J. S., Kim, S. Y., Thomas, S. R., Wardwell, L., Johnson, L. A., Emery, C. M., Stransky, N., Cogdill, A. P., Barretina, J., Caponigro, G., Hieronymus, H., Murray, R. R., Salehi-Ashtiani, K., Hill, D. E., Vidal, M., Zhao, J. J., Yang, X., Alkan, O., Kim, S., Harris, J. L., Wilson, C. J., Myer, V. E., Finan, P. M., Root, D. E., Roberts, T. M., Golub, T., Flaherty, K. T., Dummer, R., Weber, B. L., Sellers, W. R., Schlegel, R., Wargo, J. A., Hahn, W. C., and Garraway, L. A. (2010) COT drives resistance to RAF inhibition through MAP kinase pathway reactivation. Nature 468, 968-972
68. Haass, N. K., Sproesser, K., Nguyen, T. K., Contractor, R., Medina, C. A., Nathanson, K. L., Herlyn, M., and Smalley, K. S. M. (2008) The mitogenactivated protein/extracellular signal-regulated kinase kinase inhibitor AZD6244 (ARRY-142886) induces growth arrest in melanoma cells and tumor regression when combined with docetaxel. Clin. Cancer Res. 14, 230-239
69. Collisson, E. A., De, A., Suzuki, H., Gambhir, S. S., and Kolodney, M. S. (2003) Treatment of metastatic melanoma with an orally available inhibitor of the Ras-Raf-MAPK cascade. Cancer Res. 63, 5669-5673
70. Wang, D., Boerner, S. A., Winkler, J. D., and LoRusso, P. M. (2007) Clinical experience of MEK inhibitors in cancer therapy. Biochim. Biophys. Acta 1773, 1248-1255
71. Beltrao, P., Bork, P., Krogan, N. J., and van Noort, V. (2013) Evolution and functional cross-talk of protein post-translational modifications. Mol. Syst. Biol. 9, 714
72. Beltrao, P., Albanè se, V., Kenner, L. R., Swaney, D. L., Burlingame, A., Villén, J., Lim, W. A., Fraser, J. S., Frydman, J., and Krogan, N. J. (2012) Systematic functional prioritization of protein posttranslational modifications. Cell 150, 413-425
73. Micallef, L., and Rodgers, P. (2014) eulerAPE: drawing area-proportional 3-Venn diagrams using ellipses. PLoS One 9, e101717