TAILS N-Terminomics and Proteomics Show Protein Degradation Dominates over Proteolytic Processing by Cathepsins in Pancreatic Tumors

Cell Reports

Volumn 16, Issue 6, 2016, Pages 1762-1773

  Prudova, Anna ^a   Gocheva, Vasilena ^b   auf dem Keller, Ulrich ^a   Eckhard, Ulrich ^a   Olson, Oakley C ^b   Akkari, Leila ^c,d   Butler, Georgina S ^a   Fortelny, Nikolaus ^a   Lange, Philipp F ^a   Mark, Jennifer C ^a   Joyce, Johanna A ^b,c,d   Overall, Christopher M ^a  

^a UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^b MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

^c LUDWIG INSTITUTE FOR CANCER RESEARCH   (Switzerland)

^d UNIVERSITY OF LAUSANNE   (Switzerland)

Author keywords

cysteine cathepsins; degradation; ECM; lysosomal hydrolases; pancreatic neuroendocrine cancer; proteases; proteolytic processing; proteomics; substrate discovery; TAILS degradomics

Indexed keywords

CATHEPSIN; CATHEPSIN B; CATHEPSIN H; CATHEPSIN L; CATHEPSIN S; CATHEPSIN X; GLUCOSE REGULATED PROTEIN 78; PROTHYMOSIN ALPHA; PYRUVATE KINASE; HEAT SHOCK PROTEIN; MOLECULAR CHAPERONE GRP78; ONCOPROTEIN; PROTEOME;

AMINO TERMINAL SEQUENCE; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CARCINOGENESIS; CONTROLLED STUDY; MASS SPECTROMETRY; MOUSE; NONHUMAN; PANCREATIC NEUROENDOCRINE TUMOR; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN CLEAVAGE; PROTEIN DEGRADATION; PROTEIN FUNCTION; PROTEIN PROCESSING; PROTEOMICS; REGULATORY MECHANISM; SEQUENCE ANALYSIS; SIGNAL TRANSDUCTION; TERMINAL AMINE ISOTOPIC LABELING OF SUBSTRATES; TUMOR MICROENVIRONMENT; TUMOR VOLUME; ANIMAL; ENZYME SPECIFICITY; METABOLISM; PANCREAS TUMOR; PHYSIOLOGY; PROCEDURES; TRANSGENIC MOUSE;

ANIMALS; CARCINOGENESIS; CATHEPSINS; HEAT-SHOCK PROTEINS; MICE, TRANSGENIC; ONCOGENE PROTEINS; PANCREATIC NEOPLASMS; PROTEIN PROCESSING, POST-TRANSLATIONAL; PROTEOME; PROTEOMICS; SUBSTRATE SPECIFICITY;

EID: 84979782459     PISSN: None     EISSN: 22111247     Source Type: Journal    
DOI: 10.1016/j.celrep.2016.06.086     Document Type: Article

References (53)

1. Affara, N.I., Andreu, P., Coussens, L.M., Delineating protease functions during cancer development. Methods Mol. Biol. 539 (2009), 1–32.
2. Akkari, L., Gocheva, V., Kester, J.C., Hunter, K.E., Quick, M.L., Sevenich, L., Wang, H.-W., Peters, C., Tang, L.H., Klimstra, D.S., et al. Distinct functions of macrophage-derived and cancer cell-derived cathepsin Z combine to promote tumor malignancy via interactions with the extracellular matrix. Genes Dev. 28 (2014), 2134–2150.
3. Akkari, L., Gocheva, V., Quick, M.L., Kester, J.C., Spencer, A.K., Garfall, A.L., Bowman, R.L., Joyce, J.A., Combined deletion of cathepsin protease family members reveals compensatory mechanisms in cancer. Genes Dev. 30 (2016), 220–232.
4. Anastasiou, D., Yu, Y., Israelsen, W.J., Jiang, J.-K., Boxer, M.B., Hong, B.S., Tempel, W., Dimov, S., Shen, M., Jha, A., et al. Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis. Nat. Chem. Biol. 8 (2012), 839–847.
5. auf dem Keller, U., Overall, C.M., CLIPPER: an add-on to the Trans-Proteomic Pipeline for the automated analysis of TAILS N-terminomics data. Biol. Chem. 393 (2012), 1477–1483.
6. auf dem Keller, U., Prudova, A., Gioia, M., Butler, G.S., Overall, C.M., A statistics-based platform for quantitative N-terminome analysis and identification of protease cleavage products. Mol. Cell. Proteomics 9 (2010), 912–927.
7. auf dem Keller, U., Prudova, A., Eckhard, U., Fingleton, B., Overall, C.M., Systems-level analysis of proteolytic events in increased vascular permeability and complement activation in skin inflammation. Sci. Signal., 6, 2013, rs2.
8. Benavides, F., Perez, C., Blando, J., Contreras, O., Shen, J., Coussens, L.M., Fischer, S.M., Kusewitt, D.F., DiGiovanni, J., Conti, C.J., Protective role of cathepsin L in mouse skin carcinogenesis. Mol. Carcinog. 51 (2012), 352–361.
9. Biasini, M., Bienert, S., Waterhouse, A., Arnold, K., Studer, G., Schmidt, T., Kiefer, F., Gallo Cassarino, T., Bertoni, M., Bordoli, L., Schwede, T., SWISS-MODEL: modelling protein tertiary and quaternary structure using evolutionary information. Nucleic Acids Res. 42 (2014), W252–W2588.
10. Biniossek, M.L., Nägler, D.K., Becker-Pauly, C., Schilling, O., Proteomic identification of protease cleavage sites characterizes prime and non-prime specificity of cysteine cathepsins B, L, and S. J. Proteome Res. 10 (2011), 5363–5373.
11. DeLano, W.L., The case for open-source software in drug discovery. Drug Discov. Today 10 (2005), 213–217.
12. Dennemärker, J., Lohmüller, T., Mayerle, J., Tacke, M., Lerch, M.M., Coussens, L.M., Peters, C., Reinheckel, T., Deficiency for the cysteine protease cathepsin L promotes tumor progression in mouse epidermis. Oncogene 29 (2010), 1611–1621.
13. Dombrauckas, J.D., Santarsiero, B.D., Mesecar, A.D., Structural basis for tumor pyruvate kinase M2 allosteric regulation and catalysis. Biochemistry 44 (2005), 9417–9429.
14. Eckhard, U., Marino, G., Abbey, S.R., Tharmarajah, G., Matthew, I., Overall, C.M., The human dental pulp proteome and N-terminome: levering the unexplored potential of semitryptic peptides enriched by TAILS to identify missing proteins in the Human Proteome Project in underexplored tissues. J. Proteome Res. 14 (2015), 3568–3582.
15. Evstafieva, A.G., Belov, G.A., Kalkum, M., Chichkova, N.V., Bogdanov, A.A., Agol, V.I., Vartapetian, A.B., Prothymosin alpha fragmentation in apoptosis. FEBS Lett. 467 (2000), 150–154.
16. Filipp, F.V., Cancer metabolism meets systems biology: pyruvate kinase isoform PKM2 is a metabolic master regulator. J. Carcinog., 12, 2013, 14.
17. Fortelny, N., Yang, S., Pavlidis, P., Lange, P.F., Overall, C.M., Proteome TopFIND 3.0 with TopFINDer and PathFINDer: database and analysis tools for the association of protein termini to pre- and post-translational events. Nucleic Acids Res. 43 (2015), D290–D297.
18. Gocheva, V., Zeng, W., Ke, D., Klimstra, D., Reinheckel, T., Peters, C., Hanahan, D., Joyce, J.A., Distinct roles for cysteine cathepsin genes in multistage tumorigenesis. Genes Dev. 20 (2006), 543–556.
19. Gocheva, V., Chen, X., Peters, C., Reinheckel, T., Joyce, J.A., Deletion of cathepsin H perturbs angiogenic switching, vascularization and growth of tumors in a mouse model of pancreatic islet cell cancer. Biol. Chem. 391 (2010), 937–945.
20. Goulet, B., Baruch, A., Moon, N.-S., Poirier, M., Sansregret, L.L., Erickson, A., Bogyo, M., Nepveu, A., A cathepsin L isoform that is devoid of a signal peptide localizes to the nucleus in S phase and processes the CDP/Cux transcription factor. Mol. Cell 14 (2004), 207–219.
21. Hanahan, D., Heritable formation of pancreatic beta-cell tumours in transgenic mice expressing recombinant insulin/simian virus 40 oncogenes. Nature 315 (1985), 115–122.
22. Hasan, L., Mazzucchelli, L., Liebi, M., Lis, M., Hunger, R.E., Tester, A., Overall, C.M., Wolf, M., Function of liver activation-regulated chemokine/CC chemokine ligand 20 is differently affected by cathepsin B and cathepsin D processing. J. Immunol. 176 (2006), 6512–6522.
23. Jiang, X., Kim, H.-E., Shu, H., Zhao, Y., Zhang, H., Kofron, J., Donnelly, J., Burns, D., Ng, S.-C., Rosenberg, S., Wang, X., Distinctive roles of PHAP proteins and prothymosin-alpha in a death regulatory pathway. Science 299 (2003), 223–226.
24. Jiang, J., Prasad, K., Lafer, E.M., Sousa, R., Structural basis of interdomain communication in the Hsc70 chaperone. Mol. Cell 20 (2005), 513–524.
25. Joyce, J.A., Baruch, A., Chehade, K., Meyer-Morse, N., Giraudo, E., Tsai, F.-Y., Greenbaum, D.C., Hager, J.H., Bogyo, M., Hanahan, D., Cathepsin cysteine proteases are effectors of invasive growth and angiogenesis during multistage tumorigenesis. Cancer Cell 5 (2004), 443–453.
26. Kallunki, T., Olsen, O.D., Jäättelä, M., Cancer-associated lysosomal changes: friends or foes?. Oncogene 32 (2013), 1995–2004.
27. Kleifeld, O., Doucet, A., auf dem Keller, U., Prudova, A., Schilling, O., Kainthan, R.K., Starr, A.E., Foster, L.J., Kizhakkedathu, J.N., Overall, C.M., Isotopic labeling of terminal amines in complex samples identifies protein N-termini and protease cleavage products. Nat. Biotechnol. 28 (2010), 281–288.
28. Kleifeld, O., Doucet, A., Prudova, A., auf dem Keller, U., Gioia, M., Kizhakkedathu, J.N., Overall, C.M., Identifying and quantifying proteolytic events and the natural N terminome by terminal amine isotopic labeling of substrates. Nat. Protoc. 6 (2011), 1578–1611.
29. Letsas, K.P., Frangou-Lazaridis, M., Surfing on prothymosin alpha proliferation and anti-apoptotic properties. Neoplasma 53 (2006), 92–96.
30. Luo, B., Lee, A.S., The critical roles of endoplasmic reticulum chaperones and unfolded protein response in tumorigenesis and anticancer therapies. Oncogene 32 (2013), 805–818.
31. Manrow, R.E., Sburlati, A.R., Hanover, J.A., Berger, S.L., Nuclear targeting of prothymosin alpha. J. Biol. Chem. 266 (1991), 3916–3924.
32. Melzer, I.M., Fernández, S.B.M., Bösser, S., Lohrig, K., Lewandrowski, U., Wolters, D., Kehrloesser, S., Brezniceanu, M.-L., Theos, A.C., Irusta, P.M., et al. The Apaf-1-binding protein Aven is cleaved by cathepsin D to unleash its anti-apoptotic potential. Cell Death Differ. 19 (2012), 1435–1445.
33. Milan, S.A., Yeo, C.J., Neuroendocrine tumors of the pancreas. Curr. Opin. Oncol. 24 (2012), 46–55.
34. Mohamed, M.M., Sloane, B.F., Cysteine cathepsins: multifunctional enzymes in cancer. Nat. Rev. Cancer 6 (2006), 764–775.
35. Olson, O.C., Joyce, J.A., Cysteine cathepsin proteases: regulators of cancer progression and therapeutic response. Nat. Rev. Cancer 15 (2015), 712–729.
36. Overall, C.M., Kleifeld, O., Tumour microenvironment - opinion: validating matrix metalloproteinases as drug targets and anti-targets for cancer therapy. Nat. Rev. Cancer 6 (2006), 227–239.
37. Pan, S., Chen, R., Reimel, B.A., Crispin, D.A., Mirzaei, H., Cooke, K., Coleman, J.F., Lane, Z., Bronner, M.P., Goodlett, D.R., et al. Quantitative proteomics investigation of pancreatic intraepithelial neoplasia. Electrophoresis 30 (2009), 1132–1144.
38. Paton, A.W., Beddoe, T., Thorpe, C.M., Whisstock, J.C., Wilce, M.C.J., Rossjohn, J., Talbot, U.M., Paton, J.C., AB5 subtilase cytotoxin inactivates the endoplasmic reticulum chaperone BiP. Nature 443 (2006), 548–552.
39. Prudova, A., auf dem Keller, U., Butler, G.S., Overall, C.M., Multiplex N-terminome analysis of MMP-2 and MMP-9 substrate degradomes by iTRAQ-TAILS quantitative proteomics. Mol. Cell. Proteomics 9 (2010), 894–911.
40. Rao, R.V., Peel, A., Logvinova, A., del Rio, G., Hermel, E., Yokota, T., Goldsmith, P.C., Ellerby, L.M., Ellerby, H.M., Bredesen, D.E., Coupling endoplasmic reticulum stress to the cell death program: role of the ER chaperone GRP78. FEBS Lett. 514 (2002), 122–128.
41. Repnik, U., Starr, A.E., Overall, C.M., Turk, B., Cysteine cathepsins activate ELR chemokines and inactivate non-ELR chemokines. J. Biol. Chem. 290 (2015), 13800–13811.
42. Rogers, L.D., Overall, C.M., Proteolytic post-translational modification of proteins: proteomic tools and methodology. Mol. Cell. Proteomics 12 (2013), 3532–3542.
43. Rothberg, J.M., Bailey, K.M., Wojtkowiak, J.W., Ben-Nun, Y., Bogyo, M., Weber, E., Moin, K., Blum, G., Mattingly, R.R., Gillies, R.J., Sloane, B.F., Acid-mediated tumor proteolysis: contribution of cysteine cathepsins. Neoplasia 15 (2013), 1125–1137.
44. Ruffell, B., Affara, N.I., Cottone, L., Junankar, S., Johansson, M., DeNardo, D.G., Korets, L., Reinheckel, T., Sloane, B.F., Bogyo, M., Coussens, L.M., Cathepsin C is a tissue-specific regulator of squamous carcinogenesis. Genes Dev. 27 (2013), 2086–2098.
45. Sevenich, L., Joyce, J.A., Pericellular proteolysis in cancer. Genes Dev. 28 (2014), 2331–2347.
46. Sevenich, L., Schurigt, U., Sachse, K., Gajda, M., Werner, F., Müller, S., Vasiljeva, O., Schwinde, A., Klemm, N., Deussing, J., et al. Synergistic antitumor effects of combined cathepsin B and cathepsin Z deficiencies on breast cancer progression and metastasis in mice. Proc. Natl. Acad. Sci. USA 107 (2010), 2497–2502.
47. Sevenich, L., Bowman, R.L., Mason, S.D., Quail, D.F., Rapaport, F., Elie, B.T., Brogi, E., Brastianos, P.K., Hahn, W.C., Holsinger, L.J., et al. Analysis of tumour- and stroma-supplied proteolytic networks reveals a brain-metastasis-promoting role for cathepsin S. Nat. Cell Biol. 16 (2014), 876–888.
48. Sobotič, B., Vizovišek, M., Vidmar, R., Van Damme, P., Gocheva, V., Joyce, J.A., Gevaert, K., Turk, V., Turk, B., Fonović, M., Proteomic identification of cysteine cathepsin substrates shed from the surface of cancer cells. Mol. Cell. Proteomics 14 (2015), 2213–2228.
49. Turk, V., Stoka, V., Vasiljeva, O., Renko, M., Sun, T., Turk, B., Turk, D., Cysteine cathepsins: from structure, function and regulation to new frontiers. Biochim. Biophys. Acta 1824 (2012), 68–88.
50. Van Damme, P., Maurer-Stroh, S., Plasman, K., Van Durme, J., Colaert, N., Timmerman, E., De Bock, P.-J., Goethals, M., Rousseau, F., Schymkowitz, J., et al. Analysis of protein processing by N-terminal proteomics reveals novel species-specific substrate determinants of granzyme B orthologs. Mol. Cell. Proteomics 8 (2009), 258–272.
51. Vasiljeva, O., Korovin, M., Gajda, M., Brodoefel, H., Bojic, L., Krüger, A., Schurigt, U., Sevenich, L., Turk, B., Peters, C., Reinheckel, T., Reduced tumour cell proliferation and delayed development of high-grade mammary carcinomas in cathepsin B-deficient mice. Oncogene 27 (2008), 4191–4199.
52. Wang, B., Sun, J., Kitamoto, S., Yang, M., Grubb, A., Chapman, H.A., Kalluri, R., Shi, G.-P., Cathepsin S controls angiogenesis and tumor growth via matrix-derived angiogenic factors. J. Biol. Chem. 281 (2006), 6020–6029.
53. Yang, W., Lu, Z., Regulation and function of pyruvate kinase M2 in cancer. Cancer Lett. 339 (2013), 153–158.