Double deficiency of cathepsins B and L results in massive secretome alterations and suggests a degradative cathepsin-MMP axis

Cellular and Molecular Life Sciences

Volumn 71, Issue 5, 2014, Pages 899-916

  Tholen, Stefan ^a   Biniossek, Martin L ^a   Gansz, Martina ^a   Ahrens, Theresa D ^a   Schlimpert, Manuel ^a   Kizhakkedathu, Jayachandran N ^b   Reinheckel, Thomas ^a   Schilling, Oliver ^a  

^a UNIVERSITY OF FREIBURG   (Germany)

^b UNIVERSITY OF BRITISH COLUMBIA   (Canada)

Author keywords

Cathepsin B; Cathepsin L; MMP 2; Proteolysis; Proteomics; TAILS

Indexed keywords

ANIMALS; BLOTTING, WESTERN; CATHEPSIN B; CATHEPSIN L; CELL PROLIFERATION; CELL SURVIVAL; CELLS, CULTURED; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; CHROMATOGRAPHY, ION EXCHANGE; COLLAGEN TYPE I; FIBROBLASTS; FLOW CYTOMETRY; GENE EXPRESSION REGULATION; HYDROGEN-ION CONCENTRATION; MATRIX METALLOPROTEINASE 2; MICE; MICE, KNOCKOUT; PROTEOLYSIS; TANDEM MASS SPECTROMETRY;

EID: 84893850175     PISSN: 1420682X     EISSN: 14209071     Source Type: Journal    
DOI: 10.1007/s00018-013-1406-1     Document Type: Article

References (74)

1. Turk V, Turk B, Turk D (2001) Lysosomal cysteine proteases: facts and opportunities. EMBO J 20(17):4629-4633. doi:10.109 3/emboj/20.17.4629
2. Rawlings ND, Barrett AJ, Bateman A (2010) MEROPS: the peptidase database. Nucleic Acids Res 38 (Database issue):D227-233. doi:10.1093/nar/gkp971
3. Aronson NN Jr, Barrett AJ (1978) The specificity of cathepsin B. Hydrolysis of glucagon at the C-terminus by a peptidyldipeptidase mechanism. Biochem J 171(3):759-765
4. Barbarin A, Frade R (2011) Procathepsin L secretion, which triggers tumor progression, is regulated by Rab4A in human melanoma cells. Biochem J. doi:10.1042/BJ20110361
5. Joyce JA, Baruch A, Chehade K, Meyer-Morse N, Giraudo E, Tsai FY, Greenbaum DC, Hager JH, Bogyo M, Hanahan D (2004) Cathepsin cysteine proteases are effectors of invasive growth and angiogenesis during multistage tumorigenesis. Cancer Cell 5(5):443-453
6. Jane DT, Morvay L, Dasilva L, Cavallo-Medved D, Sloane BF, Dufresne MJ (2006) Cathepsin B localizes to plasma membrane caveolae of differentiating myoblasts and is secreted in an active form at physiological pH. Biol Chem 387(2):223-234. doi:10.15 15/BC.2006.030
7. Brix K, Dunkhorst A, Mayer K, Jordans S (2008) Cysteine cathepsins: cellular roadmap to different functions. Biochimie 90(2):194-207. doi:10.1016/j.biochi.2007.07.024
8. Mohamed MM, Sloane BF (2006) Cysteine cathepsins: multifunctional enzymes in cancer. Nat Rev Cancer 6(10):764-775. doi:10.1038/nrc1949
9. Reiser J, Adair B, Reinheckel T (2010) Specialized roles for cysteine cathepsins in health and disease. J Clin Invest 120(10):3421-3431. doi:10.1172/JCI42918
10. Gocheva V, Zeng W, Ke D, Klimstra D, Reinheckel T, Peters C, Hanahan D, Joyce JA (2006) Distinct roles for cysteine cathepsin genes in multistage tumorigenesis. Genes Dev 20(5):543-556. doi:10.1101/gad.1407406
11. Sevenich L, Werner F, Gajda M, Schurigt U, Sieber C, Muller S, Follo M, Peters C, Reinheckel T (2011) Transgenic expression of human cathepsin B promotes progression and metastasis of polyoma-middle-T-induced breast cancer in mice. Oncogene 30(1):54-64. doi:10.1038/onc.2010.387
12. Greenbaum D, Luscombe NM, Jansen R, Qian J, Gerstein M (2001) Interrelating different types of genomic data, from proteome to secretome: 'oming in on function. Genome Res 11(9):1463-1468. doi:10.1101/gr.207401
13. Tholen S, Biniossek ML, Gessler AL, Muller S, Weisser J, Kizhakkedathu JN, Reinheckel T, Schilling O (2011) Contribution of cathepsin L to secretome composition and cleavage pattern of mouse embryonic fibroblasts. Biol Chem 392(11):961-971. doi: 10.1515/BC.2011.162
14. Tholen S, Biniossek ML, Gansz M, Gomez-Auli A, Werner F, Noel A, Kizhakkedathu JN, Boerries M, Busch H, Reinheckel T, Schilling O (2012) Deletion of cysteine cathepsins B or L yields differential impacts on murine skin proteome and degradome. Mol Cell Proteomics. doi:10.1074/mcp. M112.017962
15. Felbor U, Kessler B, Mothes W, Goebel HH, Ploegh HL, Bronson RT, Olsen BR (2002) Neuronal loss and brain atrophy in mice lacking cathepsins B and L. Proc Natl Acad Sci USA 99(12):7883-7888. doi:10.1073/pnas.112632299
16. Koike M, Shibata M, Waguri S, Yoshimura K, Tanida I, Kominami E, Gotow T, Peters C, Von Figura K, Mizushima N, Saftig P, Uchiyama Y (2005) Participation of autophagy in storage of lysosomes in neurons from mouse models of neuronal ceroidlipofuscinoses (Batten disease). Am J Pathol 167(6):1713-1728. doi:10.1016/S0002-9440 (10) 61253-9
17. Stahl S, Reinders Y, Asan E, Mothes W, Conzelmann E, Sickmann A, Felbor U (2007) Proteomic analysis of cathepsin Band L-deficient mouse brain lysosomes. Biochim Biophys Acta 1774(10):1237-1246. doi:10.1016/j.bbapap. 2007.07.004
18. Boersema PJ, Raijmakers R, Lemeer S, Mohammed S, Heck AJ (2009) Multiplex peptide stable isotope dimethyl labeling for quantitative proteomics. Nat Protoc 4(4):484-494. doi:10.1038/n prot.2009.21
19. Guo K, Ji C, Li L (2007) Stable-isotope dimethylation labeling combined with LC-ESI MS for quantification of amine-containing metabolites in biological samples. Anal Chem 79(22):8631-8638. doi:10.1021/ac0704356
20. Kleifeld O, Doucet A, Auf Dem Keller U, Prudova A, Schilling O, Kainthan RK, Starr AE, Foster LJ, Kizhakkedathu JN, Overall CM (2010) Isotopic labeling of terminal amines in complex samples identifies protein N-termini and protease cleavage products. Nat Biotechnol 28(3):281-288. doi:10.1038/nbt.1611
21. Molloy MP, Brzezinski EE, Hang J, McDowell MT, Van Bogelen RA (2003) Overcoming technical variation and biological variation in quantitative proteomics. Proteomics 3(10):1912-1919. doi:10.1002/pmic.200300534
22. Dennemarker J, Lohmuller T, Muller S, Aguilar SV, Tobin DJ, Peters C, Reinheckel T (2010) Impaired turnover of autophagolysosomes in cathepsin L deficiency. Biol Chem 391(8):913-922. doi:10.1515/BC.2010.097
23. Morgenstern JP, Land H (1990) Advanced mammalian gene transfer: high titre retroviral vectors with multiple drug selection markers and a complementary helper-free packaging cell line. Nucleic Acids Res 18(12):3587-3596
24. Soneoka Y, Cannon PM, Ramsdale EE, Griffiths JC, Romano G, Kingsman SM, Kingsman AJ (1995) A transient three-plasmid expression system for the production of high titer retroviral vectors. Nucleic Acids Res 23(4):628-633
25. Pedrioli PG, Eng JK, Hubley R, Vogelzang M, Deutsch EW, Raught B, Pratt B, Nilsson E, Angeletti RH, Apweiler R, Cheung K, Costello CE, Hermjakob H, Huang S, Julian RK, Kapp E, McComb ME, Oliver SG, Omenn G, Paton NW, Simpson R, Smith R, Taylor CF, Zhu W, Aebersold R (2004) A common open representation of mass spectrometry data and its application to proteomics research. Nat Biotechnol 22(11):1459-1466. doi:10.1038/nbt1031
26. Kessner D, Chambers M, Burke R, Agus D, Mallick P (2008) ProteoWizard: open source software for rapid proteomics tools development. Bioinformatics 24(21):2534-2536. doi:10.1093/bioinformatics/btn323
27. Craig R, Beavis RC (2004) TA NDEM: matching proteins with tandem mass spectra. Bioinformatics 20(9):1466-1467. doi:10.1093/bioinformatics/bth092
28. Keller A, Nesvizhskii AI, Kolker E, Aebersold R (2002) Empirical statistical model to estimate the accuracy of peptide identifications made by MS/MS and database search. Anal Chem 74(20):5383-5392
29. Cochrane GR (2010) The Universal Protein Resource (UniProt) in 2010. Nucleic Acids Res 38 (Database issue):D142-148. doi:10.1093/nar/gkp846
30. Martens L, Vandekerckhove J, Gevaert K (2005) DBToolkit: processing protein databases for peptide-centric proteomics. Bioinformatics 21(17):3584-3585. doi:10.1093/bioinformatics/bti588
31. Li XJ, Zhang H, Ranish JA, Aebersold R (2003) Automated statistical analysis of protein abundance ratios from data generated by stable-isotope dilution and tandem mass spectrometry. Anal Chem 75(23):6648-6657. doi:10.1021/ac034633i
32. Mo F, Mo Q, Chen Y, Goodlett DR, Hood L, Omenn GS, Li S, Lin B (2010) WaveletQuant, an improved quantification software based on wavelet signal threshold de-noising for labeled quantitative proteomic analysis. BMC Bioinform 11:219. doi:10.1186/1471-2105-11-219
33. Han DK, Eng J, Zhou H, Aebersold R (2001) Quantitative profiling of differentiation-induced microsomal proteins using isotopecoded affinity tags and mass spectrometry. Nat Biotechnol 19(10):946-951. doi:10.1038/nbt1001-946
34. Kleifeld O, Doucet A, Prudova A, Auf Dem Keller U, Gioia M, Kizhakkedathu J, Overall CM (2011) System-wide proteomic identification of protease cleavage products by terminal amine isotopic labeling of substrates. Nat Prot 6(10):1578-1611. doi:10. 1038/nprot.2011.382
35. Rappsilber J, Ishihama Y, Mann M (2003) Stop and go extraction tips for matrix-assisted laser desorption/ionization, nanoelectrospray, and LC/MS sample pretreatment in proteomics. Anal Chem 75(3):663-670
36. Pan C, Kumar C, Bohl S, Klingmueller U, Mann M (2009) Comparative proteomic phenotyping of cell lines and primary cells to assess preservation of cell type-specific functions. Mol Cell Proteomics 8(3):443-450. doi:10.1074/mcp. M800258-MCP200
37. Olsen JV, Ong SE, Mann M (2004) Trypsin cleaves exclusively C-terminal to arginine and lysine residues. Mol Cell Proteomics 3(6):608-614. doi:10.1074/mcp. T400003-MCP200
38. Stypmann J, Glaser K, Roth W, Tobin DJ, Petermann I, Matthias R, Monnig G, Haverkamp W, Breithardt G, Schmahl W, Peters C, Reinheckel T (2002) Dilated cardiomyopathy in mice deficient for the lysosomal cysteine peptidase cathepsin L. Proc Natl Acad Sci USA 99(9):6234-6239. doi:10.1073/pnas.092637699
39. Petermann I, Mayer C, Stypmann J, Biniossek ML, Tobin DJ, Engelen MA, Dandekar T, Grune T, Schild L, Peters C, Reinheckel T (2006) Lysosomal, cytoskeletal, and metabolic alterations in cardiomyopathy of cathepsin L knockout mice. Faseb J 20(8):1266-1268. doi:10.1096/fj.05-5517fje
40. Friedrichs B, Tepel C, Reinheckel T, Deussing J, Von Figura K, Herzog V, Peters C, Saftig P, Brix K (2003) Thyroid functions of mouse cathepsins B, K, and L. J Clin Invest 111(11):1733-1745. doi:10.1172/JCI15990
41. Tobin DJ, Foitzik K, Reinheckel T, Mecklenburg L, Botchkarev VA, Peters C, Paus R (2002) The lysosomal protease cathepsin L is an important regulator of keratinocyte and melanocyte differentiation during hair follicle morphogenesis and cycling. Am J Pathol 160(5):1807-1821. doi:10.1016/S0002-9440 (10) 61127-3
42. Dean RA, Overall CM (2007) Proteomics discovery of metalloproteinase substrates in the cellular context by iTRAQ labeling reveals a diverse MMP-2 substrate degradome. Mol Cell Proteomics 6(4):611-623. doi:10.1074/mcp. M600341-MCP200
43. Planque C, Kulasingam V, Smith CR, Reckamp K, Goodglick L, Diamandis EP (2009) Identification of five candidate lung cancer biomarkers by proteomics analysis of conditioned media of four lung cancer cell lines. Mol Cell Proteomics 8(12):2746-2758. doi:10.1074/mcp. M900134-MCP200
44. Xu BJ, Yan W, Jovanovic B, An AQ, Cheng N, Aakre ME, Yi Y, Eng J, Link AJ, Moses HL (2010) Quantitative analysis of the secretome of TGF-beta signaling-deficient mammary fibroblasts. Proteomics 10(13):2458-2470. doi:10.1002/pmic.200900701
45. Makawita S, Smith C, Batruch I, Zheng Y, Ruckert F, Grutzmann R, Pilarsky C, Gallinger S, Diamandis EP (2011) Integrated proteomic profiling of cell line conditioned media and pancreatic juice for the identification of pancreatic cancer biomarkers. Mol Cell Proteomics 10(10):M111-008599. doi:10.1074/mcp. M111.008599
46. Auf Dem Keller U, Schilling O (2010) Proteomic techniques and activity-based probes for the system-wide study of proteolysis. Biochimie 92(11):1705-1714. doi:10.1016/j.biochi.2010.04.027
47. Prudova A, Auf Dem Keller U, Butler GS, Overall CM (2010) Multiplex N-terminome analysis of MMP-2 and MMP-9 substrate degradomes by iTRAQ-TA ILS quantitative proteomics. Mol Cell Proteomics 9(5):894-911. doi:10.1074/mcp. M000050-MCP201
48. Buck MR, Karustis DG, Day NA, Honn KV, Sloane BF (1992) Degradation of extracellular-matrix proteins by human cathepsin B from normal and tumour tissues. Biochem J 282 (Pt 1):273-278
49. Creemers LB, Hoeben KA, Jansen DC, Buttle DJ, Beertsen W, Everts V (1998) Participation of intracellular cysteine proteinases, in particular cathepsin B, in degradation of collagen in periosteal tissue explants. Matrix Biol 16(9):575-584
50. Guinec N, Dalet-Fumeron V, Pagano M (1993) "In vitro" study of basement membrane degradation by the cysteine proteinases, cathepsins B, B-like and L. Digestion of collagen IV, laminin, fibronectin, and release of gelatinase activities from basement membrane fibronectin. Biol Chem Hoppe Seyler 374(12):1135-1146
51. Vasiljeva O, Korovin M, Gajda M, Brodoefel H, Bojic L, Kruger A, Schurigt U, Sevenich L, Turk B, Peters C, Reinheckel T (2008) Reduced tumour cell proliferation and delayed development of high-grade mammary carcinomas in cathepsin B-deficient mice. Oncogene 27(30):4191-4199. doi:10.1038/onc.2008.59
52. Schilling O, Overall CM (2008) Proteome-derived, databasesearchable peptide libraries for identifying protease cleavage sites. Nat Biotechnol 26(6):685-694. doi:10.1038/nbt1408
53. Schilling O, Auf Dem Keller U, Overall CM (2011) Factor Xa subsite mapping by proteome-derived peptide libraries improved using WebPICS, a resource for proteomic identification of cleavage sites. Biol Chem 392(11):1031-1037. doi:10.1515/BC.2011.158
54. Schilling O, Huesgen PF, Barre O, Auf Dem Keller U, Overall CM (2011) Characterization of the prime and non-prime active site specificities of proteases by proteome-derived peptide libraries and tandem mass spectrometry. Nat Protoc 6(1):111-120. doi: 10.1038/nprot.2010.178
55. Biniossek ML, Nagler DK, Becker-Pauly C, Schilling O (2011) Proteomic identification of protease cleavage sites characterizes prime and non-prime specificity of cysteine cathepsins B, L, and S. J Proteome Res 10(12):5363-5373. doi:10.1021/pr200621z
56. Bernhardt A, Kuester D, Roessner A, Reinheckel T, Krueger S (2010) Cathepsin X-deficient gastric epithelial cells in co-culture with macrophages: characterization of cytokine response and migration capability after Helicobacter pylori infection. J Biol Chem 285(44):33691-33700. doi:10.1074/jbc. M110.146183
57. Sevenich L, Schurigt U, Sachse K, Gajda M, Werner F, Muller S, Vasiljeva O, Schwinde A, Klemm N, Deussing J, Peters C, Reinheckel T (2010) 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(6):2497-2502. doi:10.1073/pnas.0907240107
58. Wille A, Gerber A, Heimburg A, Reisenauer A, Peters C, Saftig P, Reinheckel T, Welte T, Buhling F (2004) Cathepsin L is involved in cathepsin D processing and regulation of apoptosis in A549 human lung epithelial cells. Biol Chem 385(7):665-670. doi:10. 1515/BC.2004.082
59. Szklarczyk D, Franceschini A, Kuhn M, Simonovic M, Roth A, Minguez P, Doerks T, Stark M, Muller J, Bork P, Jensen LJ, Von Mering C (2011) The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored. Nucleic Acids Res 39 (Database issue):D561-568. doi:10.1093/na r/gkq973
60. Valenta T, Hausmann G, Basler K (2012) The many faces and functions of beta-catenin. EMBO J 31(12):2714-2736. doi:10.10 38/emboj.2012.150
61. Adams PD, Enders GH (2008) Wnt-signaling and senescence: a tug of war in early neoplasia? Cancer Biol Ther 7(11):1706-1711
62. Caldwell GM, Jones CE, Taniere P, Warrack R, Soon Y, Matthews GM, Morton DG (2006) The Wnt antagonist sFRP1 is downregulated in premalignant large bowel adenomas. Br J Cancer 94(6):922-927. doi:10.1038/sj.bjc.6602967
63. Lah TT, Buck MR, Honn KV, Crissman JD, Rao NC, Liotta LA, Sloane BF (1989) Degradation of laminin by human tumor cathepsin B. Clin Exp Metastasis 7(4):461-468
64. Novinec M, Grass RN, Stark WJ, Turk V, Baici A, Lenarcic B (2007) Interaction between human cathepsins K, L, and S and elastins: mechanism of elastinolysis and inhibition by macromolecular inhibitors. J Biol Chem 282(11):7893-7902. doi:10.1074/jbc. M610107200
65. Malanchi I, Santamaria-Martinez A, Susanto E, Peng H, Lehr HA, Delaloye JF, Huelsken J (2012) Interactions between cancer stem cells and their niche govern metastatic colonization. Nature 481(7379):85-89. doi:10.1038/nature10694
66. Snider P, Hinton RB, Moreno-Rodriguez RA, Wang J, Rogers R, Lindsley A, Li F, Ingram DA, Menick D, Field L, Firulli AB, Molkentin JD, Markwald R, Conway SJ (2008) Periostin is required for maturation and extracellular matrix stabilization of noncardiomyocyte lineages of the heart. Circ Res 102(7):752-760. doi:10.1161/CIRCRESAHA.107.159517
67. Norris RA, Damon B, Mironov V, Kasyanov V, Ramamurthi A, Moreno-Rodriguez R, Trusk T, Potts JD, Goodwin RL, Davis J, Hoffman S, Wen X, Sugi Y, Kern CB, Mjaatvedt CH, Turner DK, Oka T, Conway SJ, Molkentin JD, Forgacs G, Markwald RR (2007) Periostin regulates collagen fibrillogenesis and the biomechanical properties of connective tissues. J Cell Biochem 101(3):695-711. doi:10.1002/jcb.21224
68. Curran S, Murray GI (1999) Matrix metalloproteinases in tumour invasion and metastasis. J Pathol 189(3):300-308. doi:10.1002/(SICI) 1096-9896 (199911) 189:3<300:AID-PATH 456>3.0. CO;2-C
69. Egeblad M, Werb Z (2002) New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2(3):161-174. doi:10.1038/nrc745
70. Loffek S, Schilling O, Franzke CW (2011) Series "matrix metalloproteinases in lung health and disease": biological role of matrix metalloproteinases: a critical balance. Eur Respir J 38(1):191-208. doi:10.1183/09031936.00146510
71. Aimes RT, Quigley JP (1995) Matrix metalloproteinase-2 is an interstitial collagenase. Inhibitor-free enzyme catalyzes the cleavage of collagen fibrils and soluble native type I collagen generating the specific 3/4- and 1/4-length fragments. J Biol Chem 270(11):5872-5876
72. Okada Y, Morodomi T, Enghild JJ, Suzuki K, Yasui A, Nakanishi I, Salvesen G, Nagase H (1990) Matrix metalloproteinase 2 from human rheumatoid synovial fibroblasts. Purification and activation of the precursor and enzymic properties. Eur J Biochem 194(3):721-730
73. Seltzer JL, Eisen AZ, Bauer EA, Morris NP, Glanville RW, Burgeson RE (1989) Cleavage of type VII collagen by interstitial collagenase and type IV collagenase (gelatinase) derived from human skin. J Biol Chem 264(7):3822-3826
74. Kersey PJ, Duarte J, Williams A, Karavidopoulou Y, Birney E, Apweiler R (2004) The International Protein Index: an integrated database for proteomics experiments. Proteomics 4(7):1985-1988. doi:10.1002/pmic.200300721