Skip to main content
View expanded cover

Proteases: Structure and Function pp 175–216Cite as

Limited and Degradative Proteolysis in the Context of Posttranslational Regulatory Networks: Current Technical and Conceptional Advances

Abstract

Proteolytic processing is a major posttranslational modification (PTM) and essential in a variety of pathological and physiological processes. Proteolysis is integrated in a complex network of multiple PTMs, such as phosphorylation, acetylation or ubiquitination, that form a strongly regulated network. Currently the investigation of the co-operative action of proteolysis with other PTMs is emerging. Recently developed proteomic and degradomic techniques enable the determination of the active site specificity of proteases, the identification of in vivo substrates as well as the elucidation of the impact of proteases to proteome composition. Activity-based probes allow for detection and localization of protease activity.

This chapter provides a comprehensive overview of proteomic and degradomic tools that characterize protease action and highlights important nodes of the proteolytic network. Moreover it illustrates how proteolysis is modulated by other PTMs, and depicts its role in protein turnover.

Keywords

  • Cleavage Site
  • Primary Amine
  • Ubiquitin Proteasome System
  • Limited Proteolysis
  • Tobacco Etch Virus

These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

This is a preview of subscription content, access via your institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • DOI: 10.1007/978-3-7091-0885-7_5
  • Chapter length: 42 pages
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
eBook
USD   169.00
Price excludes VAT (USA)
  • ISBN: 978-3-7091-0885-7
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
Softcover Book
USD   219.99
Price excludes VAT (USA)
Hardcover Book
USD   279.99
Price excludes VAT (USA)
Learn about institutional subscriptions
Fig. 5.1
Fig. 5.2
Fig. 5.3
Fig. 5.4
Fig. 5.5
Fig. 5.6
Fig. 5.7
Fig. 5.8
Fig. 5.9
Fig. 5.10
Fig. 5.11
Fig. 5.12
Fig. 5.13
Fig. 5.14

References

  • Agard NJ, Wells JA (2009) Methods for the proteomic identification of protease substrates. Curr Opin Chem Biol 13:503–509

    CAS  PubMed Central  PubMed  Google Scholar 

  • Agard NJ, Maltby D, Wells JA (2010) Inflammatory stimuli regulate caspase substrate profiles. Mol Cell Proteomics 9:880–893

    CAS  PubMed  Google Scholar 

  • Agarraberes FA, Terlecky SR, Dice JF (1997) An intralysosomal hsp70 is required for a selective pathway of lysosomal protein degradation. J Cell Biol 137:825–834

    CAS  PubMed  Google Scholar 

  • Akimov V, Rigbolt KT, Nielsen MM, Blagoev B (2011) Characterization of ubiquitination dependent dynamics in growth factor receptor signaling by quantitative proteomics. Mol Biosyst 7(12):3223–3233

    CAS  PubMed  Google Scholar 

  • Arnesen T, Van Damme P, Polevoda B, Helsens K, Evjenth R, Colaert N, Varhaug JE, Vandekerckhove J, Lillehaug JR, Sherman F et al (2009) Proteomics analyses reveal the evolutionary conservation and divergence of N-terminal acetyltransferases from yeast and humans. Proc Natl Acad Sci U S A 106:8157–8162

    CAS  PubMed Central  PubMed  Google Scholar 

  • Arntzen MO, Thiede B (2012) ApoptoProteomics, an integrated database for analysis of proteomics data obtained from apoptotic cells. Mol Cell Proteomics 11(M111):010447

    PubMed  Google Scholar 

  • Attaix D, Combaret L, Pouch MN, Taillandier D (2001) Regulation of proteolysis. Curr Opin Clin Nutr Metab Care 4:45–49

    CAS  PubMed  Google Scholar 

  • auf dem Keller U, Schilling O (2010) Proteomic techniques and activity-based probes for the system-wide study of proteolysis. Biochimie 92:1705–1714

    Google Scholar 

  • auf dem Keller U, Prudova A, Gioia M, Butler GS, Overall CM (2010) A statistics-based platform for quantitative N-terminome analysis and identification of protease cleavage products. Mol Cell Proteomics 9:912–927

    Google Scholar 

  • Beau I, Esclatine A, Codogno P (2008) Lost to translation: when autophagy targets mature ribosomes. Trends Cell Biol 18:311–314

    CAS  PubMed  Google Scholar 

  • Becker-Pauly C, Barre O, Schilling O, auf dem Keller U, Ohler A, Broder C, Schutte A, Kappelhoff R, Stocker W, Overall CM (2011) Proteomic analyses reveal an acidic prime side specificity for the astacin metalloprotease family reflected by physiological substrates. Mol Cell Proteomics 10(M111):009233

    PubMed  Google Scholar 

  • Behrends C, Sowa ME, Gygi SP, Harper JW (2010) Network organization of the human autophagy system. Nature 466:68–76

    CAS  PubMed Central  PubMed  Google Scholar 

  • Berger AB, Witte MD, Denault JB, Sadaghiani AM, Sexton KM, Salvesen GS, Bogyo M (2006) Identification of early intermediates of caspase activation using selective inhibitors and activity-based probes. Mol Cell 23:509–521

    CAS  PubMed  Google Scholar 

  • Bernales S, McDonald KL, Walter P (2006) Autophagy counterbalances endoplasmic reticulum expansion during the unfolded protein response. PLoS Biol 4:e423

    PubMed Central  PubMed  Google Scholar 

  • 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 10:5363–5373

    CAS  PubMed  Google Scholar 

  • Bitoun E, Micheloni A, Lamant L, Bonnart C, Tartaglia-Polcini A, Cobbold C, Al Saati T, Mariotti F, Mazereeuw-Hautier J, Boralevi F et al (2003) LEKTI proteolytic processing in human primary keratinocytes, tissue distribution and defective expression in Netherton syndrome. Hum Mol Genet 12:2417–2430

    CAS  PubMed  Google Scholar 

  • Blair JA, Rauh D, Kung C, Yun CH, Fan QW, Rode H, Zhang C, Eck MJ, Weiss WA, Shokat KM (2007) Structure-guided development of affinity probes for tyrosine kinases using chemical genetics. Nat Chem Biol 3:229–238

    CAS  PubMed  Google Scholar 

  • Blum G (2008) Use of fluorescent imaging to investigate pathological protease activity. Curr Opin Drug Discov Devel 11:708–716

    CAS  PubMed  Google Scholar 

  • Blum G, Mullins SR, Keren K, Fonovic M, Jedeszko C, Rice MJ, Sloane BF, Bogyo M (2005) Dynamic imaging of protease activity with fluorescently quenched activity-based probes. Nat Chem Biol 1:203–209

    CAS  PubMed  Google Scholar 

  • Blum G, von Degenfeld G, Merchant MJ, Blau HM, Bogyo M (2007) Noninvasive optical imaging of cysteine protease activity using fluorescently quenched activity-based probes. Nat Chem Biol 3:668–677

    CAS  PubMed  Google Scholar 

  • Boisvert FM, Ahmad Y, Gierlinski M, Charriere F, Lamond D, Scott M, Barton G, Lamond AI (2012) A quantitative spatial proteomics analysis of proteome turnover in human cells. Mol Cell Proteomics 11(3):M111.011429

    PubMed  Google Scholar 

  • Buschmann T, Lerner D, Lee CG, Ronai Z (2001) The Mdm-2 amino terminus is required for Mdm2 binding and SUMO-1 conjugation by the E2 SUMO-1 conjugating enzyme Ubc9. J Biol Chem 276:40389–40395

    CAS  PubMed  Google Scholar 

  • Butler GS, Overall CM (2009) Updated biological roles for matrix metalloproteinases and new “intracellular” substrates revealed by degradomics. Biochemistry 48:10830–10845

    CAS  PubMed  Google Scholar 

  • Butler GS, Butler MJ, Atkinson SJ, Will H, Tamura T, Schade van Westrum S, Crabbe T, Clements J, d’Ortho MP, Murphy G (1998) The TIMP2 membrane type 1 metalloproteinase “receptor” regulates the concentration and efficient activation of progelatinase A. A kinetic study. J Biol Chem 273:871–880

    CAS  PubMed  Google Scholar 

  • Cardoso CM, Groth-Pedersen L, Hoyer-Hansen M, Kirkegaard T, Corcelle E, Andersen JS, Jaattela M, Nylandsted J (2009) Depletion of kinesin 5B affects lysosomal distribution and stability and induces peri-nuclear accumulation of autophagosomes in cancer cells. PLoS One 4:e4424

    PubMed Central  PubMed  Google Scholar 

  • Chan EW, Chattopadhaya S, Panicker RC, Huang X, Yao SQ (2004) Developing photoactive affinity probes for proteomic profiling: hydroxamate-based probes for metalloproteases. J Am Chem Soc 126:14435–14446

    CAS  PubMed  Google Scholar 

  • Chan CP, Mak TY, Chin KT, Ng IO, Jin DY (2010) N-linked glycosylation is required for optimal proteolytic activation of membrane-bound transcription factor CREB-H. J Cell Sci 123:1438–1448

    CAS  PubMed  Google Scholar 

  • Chavanas S, Bodemer C, Rochat A, Hamel-Teillac D, Ali M, Irvine AD, Bonafe JL, Wilkinson J, Taieb A, Barrandon Y et al (2000) Mutations in SPINK5, encoding a serine protease inhibitor, cause Netherton syndrome. Nat Genet 25:141–142

    CAS  PubMed  Google Scholar 

  • Chitra S, Nalini G, Rajasekhar G (2012) The ubiquitin proteasome system and efficacy of proteasome inhibitors in diseases. Int J Rheum Dis 15:249–260

    CAS  PubMed  Google Scholar 

  • Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M (2009) Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science 325:834–840

    CAS  PubMed  Google Scholar 

  • Ciechanover A (2005) Proteolysis: from the lysosome to ubiquitin and the proteasome. Nat Rev Mol Cell Biol 6:79–87

    CAS  PubMed  Google Scholar 

  • Ciechanover A (2006) The ubiquitin proteolytic system: from an idea to the patient bed. Proc Am Thorac Soc 3:21–31

    CAS  PubMed  Google Scholar 

  • Ciechanover A, Elias S, Heller H, Ferber S, Hershko A (1980) Characterization of the heat-stable polypeptide of the ATP-dependent proteolytic system from reticulocytes. J Biol Chem 255:7525–7528

    CAS  PubMed  Google Scholar 

  • Conus S, Simon HU (2010) Cathepsins and their involvement in immune responses. Swiss Med Wkly 140:w13042

    PubMed  Google Scholar 

  • Coux O, Tanaka K, Goldberg AL (1996) Structure and functions of the 20S and 26S proteasomes. Annu Rev Biochem 65:801–847

    CAS  PubMed  Google Scholar 

  • Cox J, Mann M (2007) Is proteomics the new genomics? Cell 130:395–398

    CAS  PubMed  Google Scholar 

  • Crawford ED, Wells JA (2011) Caspase substrates and cellular remodeling. Annu Rev Biochem 80:1055–1087

    CAS  PubMed  Google Scholar 

  • Cuervo AM, Dice JF, Knecht E (1997) A population of rat liver lysosomes responsible for the selective uptake and degradation of cytosolic proteins. J Biol Chem 272:5606–5615

    CAS  PubMed  Google Scholar 

  • De Duve C, Gianetto R, Appelmans F, Wattiaux R (1953) Enzymic content of the mitochondria fraction. Nature 172:1143–1144

    Google Scholar 

  • de Godoy LM, Olsen JV, de Souza GA, Li G, Mortensen P, Mann M (2006) Status of complete proteome analysis by mass spectrometry: SILAC labeled yeast as a model system. Genome Biol 7:R50

    PubMed Central  PubMed  Google Scholar 

  • Debigare R, Price SR (2003) Proteolysis, the ubiquitin-proteasome system, and renal diseases. Am J Physiol Renal Physiol 285:F1–F8

    CAS  PubMed  Google Scholar 

  • Dengjel J, Hoyer-Hansen M, Nielsen MO, Eisenberg T, Harder LM, Schandorff S, Farkas T, Kirkegaard T, Becker AC, Schroeder S et al (2012) Identification of autophagosome-associated proteins and regulators by quantitative proteomic analysis and genetic screens. Mol Cell Proteomics 11(M111):014035

    PubMed  Google Scholar 

  • Deu E, Verdoes M, Bogyo M (2012) New approaches for dissecting protease functions to improve probe development and drug discovery. Nat Struct Mol Biol 19:9–16

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ding B, Sun Y, Huang J (2012) Overexpression of SKI oncoprotein leads to p53 degradation through regulation of MDM2 protein sumoylation. J Biol Chem 287:14621–14630

    CAS  PubMed  Google Scholar 

  • Dix MM, Simon GM, Cravatt BF (2008) Global mapping of the topography and magnitude of proteolytic events in apoptosis. Cell 134:679–691

    CAS  PubMed Central  PubMed  Google Scholar 

  • Dix MM, Simon GM, Wang C, Okerberg E, Patricelli MP, Cravatt BF (2012) Functional interplay between caspase cleavage and phosphorylation sculpts the apoptotic proteome. Cell 150:426–440

    CAS  PubMed Central  PubMed  Google Scholar 

  • Dong J, Atwood CS, Anderson VE, Siedlak SL, Smith MA, Perry G, Carey PR (2003) Metal binding and oxidation of amyloid-beta within isolated senile plaque cores: Raman microscopic evidence. Biochemistry 42:2768–2773

    CAS  PubMed  Google Scholar 

  • Doucet A, Overall CM (2008) Protease proteomics: revealing protease in vivo functions using systems biology approaches. Mol Aspects Med 29:339–358

    CAS  PubMed  Google Scholar 

  • Doucet A, Butler GS, Rodriguez D, Prudova A, Overall CM (2008) Metadegradomics: toward in vivo quantitative degradomics of proteolytic post-translational modifications of the cancer proteome. Mol Cell Proteomics 7:1925–1951

    CAS  PubMed  Google Scholar 

  • Drag M, Salvesen GS (2010) Emerging principles in protease-based drug discovery. Nat Rev Drug Discov 9:690–701

    CAS  PubMed Central  PubMed  Google Scholar 

  • Drews O, Wildgruber R, Zong C, Sukop U, Nissum M, Weber G, Gomes AV, Ping P (2007) Mammalian proteasome subpopulations with distinct molecular compositions and proteolytic activities. Mol Cell Proteomics 6:2021–2031

    CAS  PubMed  Google Scholar 

  • Dubin G (2005) Proteinaceous cysteine protease inhibitors. Cell Mol Life Sci 62:653–669

    CAS  PubMed  Google Scholar 

  • Dunn WA Jr, Cregg JM, Kiel JA, van der Klei IJ, Oku M, Sakai Y, Sibirny AA, Stasyk OV, Veenhuis M (2005) Pexophagy: the selective autophagy of peroxisomes. Autophagy 1:75–83

    CAS  PubMed  Google Scholar 

  • Edgington LE, Berger AB, Blum G, Albrow VE, Paulick MG, Lineberry N, Bogyo M (2009) Noninvasive optical imaging of apoptosis by caspase-targeted activity-based probes. Nat Med 15:967–973

    CAS  PubMed Central  PubMed  Google Scholar 

  • Edgington LE, van Raam BJ, Verdoes M, Wierschem C, Salvesen GS, Bogyo M (2012) An optimized activity-based probe for the study of caspase-6 activation. Chem Biol 19:340–352

    CAS  PubMed Central  PubMed  Google Scholar 

  • Elias JE, Gygi SP (2007) Target-decoy search strategy for increased confidence in large-scale protein identifications by mass spectrometry. Nat Methods 4:207–214

    CAS  PubMed  Google Scholar 

  • Engelke R, Becker AC, Dengjel J (2012) The degradative inventory of the cell: proteomic insights. Antioxid Redox Signal 17:803–812

    CAS  PubMed  Google Scholar 

  • Enoksson M, Li J, Ivancic MM, Timmer JC, Wildfang E, Eroshkin A, Salvesen GS, Tao WA (2007) Identification of proteolytic cleavage sites by quantitative proteomics. J Proteome Res 6:2850–2858

    CAS  PubMed  Google Scholar 

  • Etlinger JD, Goldberg AL (1977) A soluble ATP-dependent proteolytic system responsible for the degradation of abnormal proteins in reticulocytes. Proc Natl Acad Sci U S A 74:54–58

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fenn JB, Mann M, Meng CK, Wong SF, Whitehouse CM (1989) Electrospray ionization for mass spectrometry of large biomolecules. Science 246:64–71

    CAS  PubMed  Google Scholar 

  • Fonovic M, Bogyo M (2007) Activity based probes for proteases: applications to biomarker discovery, molecular imaging and drug screening. Curr Pharm Des 13:253–261

    CAS  PubMed  Google Scholar 

  • Franch HA, Sooparb S, Du J, Brown NS (2001) A mechanism regulating proteolysis of specific proteins during renal tubular cell growth. J Biol Chem 276:19126–19131

    CAS  PubMed  Google Scholar 

  • Gafni J, Ellerby LM (2002) Calpain activation in Huntington’s disease. J Neurosci 22:4842–4849

    CAS  PubMed  Google Scholar 

  • Gafni J, Hermel E, Young JE, Wellington CL, Hayden MR, Ellerby LM (2004) Inhibition of calpain cleavage of huntingtin reduces toxicity: accumulation of calpain/caspase fragments in the nucleus. J Biol Chem 279:20211–20220

    CAS  PubMed  Google Scholar 

  • Gallien S, Duriez E, Crone C, Kellmann M, Moehring T, Domon B (2012) Targeted proteomic quantification on quadrupole-orbitrap mass spectrometer. Mol Cell Proteomics 11(12):1709–1723

    PubMed  Google Scholar 

  • Gao W, Kang JH, Liao Y, Ding WX, Gambotto AA, Watkins SC, Liu YJ, Stolz DB, Yin XM (2010) Biochemical isolation and characterization of the tubulovesicular LC3-positive autophagosomal compartment. J Biol Chem 285:1371–1383

    CAS  PubMed  Google Scholar 

  • Garcia-Verdugo I, Descamps D, Chignard M, Touqui L, Sallenave JM (2010) Lung protease/anti-protease network and modulation of mucus production and surfactant activity. Biochimie 92:1608–1617

    CAS  PubMed  Google Scholar 

  • Geng M, Zhang X, Bina M, Regnier F (2001) Proteomics of glycoproteins based on affinity selection of glycopeptides from tryptic digests. J Chromatogr B Biomed Sci Appl 752:293–306

    CAS  PubMed  Google Scholar 

  • Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J (2003) Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. Nat Biotechnol 21:566–569

    CAS  PubMed  Google Scholar 

  • Gevaert K, Van Damme P, Ghesquiere B, Impens F, Martens L, Helsens K, Vandekerckhove J (2007) A la carte proteomics with an emphasis on gel-free techniques. Proteomics 7:2698–2718

    CAS  PubMed  Google Scholar 

  • Glondu M, Liaudet-Coopman E, Derocq D, Platet N, Rochefort H, Garcia M (2002) Down-regulation of cathepsin-D expression by antisense gene transfer inhibits tumor growth and experimental lung metastasis of human breast cancer cells. Oncogene 21:5127–5134

    CAS  PubMed  Google Scholar 

  • Goldberg AL, Stein R, Adams J (1995) New insights into proteasome function: from archaebacteria to drug development. Chem Biol 2:503–508

    CAS  PubMed  Google Scholar 

  • Goldberg YP, Nicholson DW, Rasper DM, Kalchman MA, Koide HB, Graham RK, Bromm M, Kazemi-Esfarjani P, Thornberry NA, Vaillancourt JP et al (1996) Cleavage of huntingtin by apopain, a proapoptotic cysteine protease, is modulated by the polyglutamine tract. Nat Genet 13:442–449

    CAS  PubMed  Google Scholar 

  • Greenbaum D, Medzihradszky KF, Burlingame A, Bogyo M (2000) Epoxide electrophiles as activity-dependent cysteine protease profiling and discovery tools. Chem Biol 7:569–581

    CAS  PubMed  Google Scholar 

  • Gygi SP, Rist B, Gerber SA, Turecek F, Gelb MH, Aebersold R (1999) Quantitative analysis of complex protein mixtures using isotope-coded affinity tags. Nat Biotechnol 17:994–999

    CAS  PubMed  Google Scholar 

  • Hagel M, Niu D, St Martin T, Sheets MP, Qiao L, Bernard H, Karp RM, Zhu Z, Labenski MT, Chaturvedi P et al (2011) Selective irreversible inhibition of a protease by targeting a noncatalytic cysteine. Nat Chem Biol 7:22–24

    CAS  PubMed  Google Scholar 

  • Hartig W, Goldhammer S, Bauer U, Wegner F, Wirths O, Bayer TA, Grosche J (2010) Concomitant detection of beta-amyloid peptides with N-terminal truncation and different C-terminal endings in cortical plaques from cases with Alzheimer’s disease, senile monkeys and triple transgenic mice. J Chem Neuroanat 40:82–92

    PubMed  Google Scholar 

  • Hay RT (2005) SUMO: a history of modification. Mol Cell 18:1–12

    CAS  PubMed  Google Scholar 

  • Hedrich J, Lottaz D, Meyer K, Yiallouros I, Jahnen-Dechent W, Stocker W, Becker-Pauly C (2010) Fetuin-A and cystatin C are endogenous inhibitors of human meprin metalloproteases. Biochemistry 49:8599–8607

    CAS  PubMed  Google Scholar 

  • Helsens K, Timmerman E, Vandekerckhove J, Gevaert K, Martens L (2008) Peptizer, a tool for assessing false positive peptide identifications and manually validating selected results. Mol Cell Proteomics 7:2364–2372

    CAS  PubMed  Google Scholar 

  • Helsens K, Martens L, Vandekerckhove J, Gevaert K (2011) Mass spectrometry-driven proteomics: an introduction. Methods Mol Biol 753:1–27

    CAS  PubMed  Google Scholar 

  • Henriksen P, Wagner SA, Weinert BT, Sharma S, Bacinskaja G, Rehman M, Juffer AH, Walther TC, Lisby M, Choudhary C (2012) Proteome-wide analysis of lysine acetylation suggests its broad regulatory scope in Saccharomyces cerevisiae. Mol Cell Proteomics 11(11):1510–1522

    PubMed  Google Scholar 

  • Herrmann JL, O’Gaora P, Gallagher A, Thole JE, Young DB (1996) Bacterial glycoproteins: a link between glycosylation and proteolytic cleavage of a 19 kDa antigen from Mycobacterium tuberculosis. EMBO J 15:3547–3554

    CAS  PubMed  Google Scholar 

  • Higdon R, Kolker E (2007) A predictive model for identifying proteins by a single peptide match. Bioinformatics 23:277–280

    CAS  PubMed  Google Scholar 

  • Hinkson IV, Elias JE (2011) The dynamic state of protein turnover: it’s about time. Trends Cell Biol 21:293–303

    CAS  PubMed  Google Scholar 

  • Hock A, Vousden KH (2010) Regulation of the p53 pathway by ubiquitin and related proteins. Int J Biochem Cell Biol 42:1618–1621

    CAS  PubMed  Google Scholar 

  • Hsiao CC, Cheng KF, Chen HY, Chou YH, Stacey M, Chang GW, Lin HH (2009) Site-specific N-glycosylation regulates the GPS auto-proteolysis of CD97. FEBS Lett 583:3285–3290

    CAS  PubMed  Google Scholar 

  • Hu L, Roth JM, Brooks P, Luty J, Karpatkin S (2008) Thrombin up-regulates cathepsin D which enhances angiogenesis, growth, and metastasis. Cancer Res 68:4666–4673

    CAS  PubMed  Google Scholar 

  • Huesgen PF, Overall CM (2012) N- and C-terminal degradomics: new approaches to reveal biological roles for plant proteases from substrate identification. Physiol Plant 145:5–17

    CAS  PubMed  Google Scholar 

  • Impens F, Van Damme P, Demol H, Van Damme J, Vandekerckhove J, Gevaert K (2008) Mechanistic insight into taxol-induced cell death. Oncogene 27:4580–4591

    CAS  PubMed  Google Scholar 

  • Impens F, Colaert N, Helsens K, Plasman K, Van Damme P, Vandekerckhove J, Gevaert K (2010) MS-driven protease substrate degradomics. Proteomics 10:1284–1296

    CAS  PubMed  Google Scholar 

  • Imperiali B, O’Connor SE (1999) Effect of N-linked glycosylation on glycopeptide and glycoprotein structure. Curr Opin Chem Biol 3:643–649

    CAS  PubMed  Google Scholar 

  • Jakoby T, van den Berg BH, Tholey A (2012) Quantitative protease cleavage site profiling using tandem-mass-tag labeling and LC-MALDI-TOF/TOF MS/MS analysis. J Proteome Res 11:1812–1820

    CAS  PubMed  Google Scholar 

  • Jayakumar A, Kang Y, Mitsudo K, Henderson Y, Frederick MJ, Wang M, El-Naggar AK, Marx UC, Briggs K, Clayman GL (2004) Expression of LEKTI domains 6-9' in the baculovirus expression system: recombinant LEKTI domains 6-9' inhibit trypsin and subtilisin A. Protein Expr Purif 35:93–101

    CAS  PubMed  Google Scholar 

  • Jayapal KP, Sui S, Philp RJ, Kok YJ, Yap MG, Griffin TJ, Hu WS (2010) Multitagging proteomic strategy to estimate protein turnover rates in dynamic systems. J Proteome Res 9:2087–2097

    CAS  PubMed  Google Scholar 

  • Jefferson T, Causevic M, auf dem Keller U, Schilling O, Isbert S, Geyer R, Maier W, Tschickardt S, Jumpertz T, Weggen S et al (2011) Metalloprotease meprin beta generates nontoxic N-terminal amyloid precursor protein fragments in vivo. J Biol Chem 286:27741–27750

    CAS  PubMed  Google Scholar 

  • Johansen T, Lamark T (2011) Selective autophagy mediated by autophagic adapter proteins. Autophagy 7:279–296

    CAS  PubMed  Google Scholar 

  • 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 5:443–453

    CAS  PubMed  Google Scholar 

  • Kalchman MA, Graham RK, Xia G, Koide HB, Hodgson JG, Graham KC, Goldberg YP, Gietz RD, Pickart CM, Hayden MR (1996) Huntingtin is ubiquitinated and interacts with a specific ubiquitin-conjugating enzyme. J Biol Chem 271:19385–19394

    CAS  PubMed  Google Scholar 

  • Kamath KS, Vasavada MS, Srivastava S (2011) Proteomic databases and tools to decipher post-translational modifications. J Proteomics 75:127–144

    CAS  PubMed  Google Scholar 

  • 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 74:5383–5392

    CAS  PubMed  Google Scholar 

  • Kessler BM, Tortorella D, Altun M, Kisselev AF, Fiebiger E, Hekking BG, Ploegh HL, Overkleeft HS (2001) Extended peptide-based inhibitors efficiently target the proteasome and reveal overlapping specificities of the catalytic beta-subunits. Chem Biol 8:913–929

    CAS  PubMed  Google Scholar 

  • Kidd D, Liu Y, Cravatt BF (2001) Profiling serine hydrolase activities in complex proteomes. Biochemistry 40:4005–4015

    CAS  PubMed  Google Scholar 

  • Kim YJ, Yi Y, Sapp E, Wang Y, Cuiffo B, Kegel KB, Qin ZH, Aronin N, DiFiglia M (2001) Caspase 3-cleaved N-terminal fragments of wild-type and mutant huntingtin are present in normal and Huntington’s disease brains, associate with membranes, and undergo calpain-dependent proteolysis. Proc Natl Acad Sci U S A 98:12784–12789

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kim I, Rodriguez-Enriquez S, Lemasters JJ (2007) Selective degradation of mitochondria by mitophagy. Arch Biochem Biophys 462:245–253

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ et al (2011) Systematic and quantitative assessment of the ubiquitin-modified proteome. Mol Cell 44:325–340

    CAS  PubMed Central  PubMed  Google Scholar 

  • King RW, Deshaies RJ, Peters JM, Kirschner MW (1996) How proteolysis drives the cell cycle. Science 274:1652–1659

    CAS  PubMed  Google Scholar 

  • Kleifeld O, Doucet A, 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 28:281–288

    CAS  PubMed  Google Scholar 

  • Klemencic I, Carmona AK, Cezari MH, Juliano MA, Juliano L, Guncar G, Turk D, Krizaj I, Turk V, Turk B (2000) Biochemical characterization of human cathepsin X revealed that the enzyme is an exopeptidase, acting as carboxymonopeptidase or carboxydipeptidase. Eur J Biochem 267:5404–5412

    CAS  PubMed  Google Scholar 

  • Komander D, Rape M (2012) The ubiquitin code. Annu Rev Biochem 81:203–229

    CAS  PubMed  Google Scholar 

  • Kraft C, Deplazes A, Sohrmann M, Peter M (2008) Mature ribosomes are selectively degraded upon starvation by an autophagy pathway requiring the Ubp3p/Bre5p ubiquitin protease. Nat Cell Biol 10:602–610

    CAS  PubMed  Google Scholar 

  • Kristensen AR, Schandorff S, Hoyer-Hansen M, Nielsen MO, Jaattela M, Dengjel J, Andersen JS (2008) Ordered organelle degradation during starvation-induced autophagy. Mol Cell Proteomics 7:2419–2428

    CAS  PubMed  Google Scholar 

  • Kumar S, Rezaei-Ghaleh N, Terwel D, Thal DR, Richard M, Hoch M, Mc Donald JM, Wullner U, Glebov K, Heneka MT et al (2011) Extracellular phosphorylation of the amyloid beta-peptide promotes formation of toxic aggregates during the pathogenesis of Alzheimer’s disease. EMBO J 30:2255–2265

    CAS  PubMed  Google Scholar 

  • Kuo YM, Emmerling MR, Woods AS, Cotter RJ, Roher AE (1997) Isolation, chemical characterization, and quantitation of A beta 3-pyroglutamyl peptide from neuritic plaques and vascular amyloid deposits. Biochem Biophys Res Commun 237:188–191

    CAS  PubMed  Google Scholar 

  • Kuo YM, Webster S, Emmerling MR, De Lima N, Roher AE (1998) Irreversible dimerization/tetramerization and post-translational modifications inhibit proteolytic degradation of A beta peptides of Alzheimer’s disease. Biochim Biophys Acta 1406:291–298

    CAS  PubMed  Google Scholar 

  • Kurokawa M, Kornbluth S (2009) Caspases and kinases in a death grip. Cell 138:838–854

    CAS  PubMed Central  PubMed  Google Scholar 

  • LaFevre-Bernt MA, Ellerby LM (2003) Kennedy’s disease. Phosphorylation of the polyglutamine-expanded form of androgen receptor regulates its cleavage by caspase-3 and enhances cell death. J Biol Chem 278:34918–34924

    CAS  PubMed  Google Scholar 

  • Lange PF, Overall CM (2011) TopFIND, a knowledgebase linking protein termini with function. Nat Methods 8:703–704

    CAS  PubMed  Google Scholar 

  • Lange PF, Huesgen PF, Overall CM (2012) TopFIND 2.0–linking protein termini with proteolytic processing and modifications altering protein function. Nucleic Acids Res 40:D351–D361

    CAS  PubMed Central  PubMed  Google Scholar 

  • Langsford ML, Gilkes NR, Singh B, Moser B, Miller RC Jr, Warren RA, Kilburn DG (1987) Glycosylation of bacterial cellulases prevents proteolytic cleavage between functional domains. FEBS Lett 225:163–167

    CAS  PubMed  Google Scholar 

  • Laurent-Matha V, Huesgen PF, Masson O, Derocq D, Prebois C, Gary-Bobo M, Lecaille F, Rebiere B, Meurice G, Orear C et al (2012) Proteolysis of cystatin C by cathepsin D in the breast cancer microenvironment. FASEB J 26(12):5172–5181

    CAS  PubMed  Google Scholar 

  • Le Magueresse-Battistoni B (2007) Serine proteases and serine protease inhibitors in testicular physiology: the plasminogen activation system. Reproduction 134:721–729

    PubMed  Google Scholar 

  • Lee MH, Lee SW, Lee EJ, Choi SJ, Chung SS, Lee JI, Cho JM, Seol JH, Baek SH, Kim KI et al (2006) SUMO-specific protease SUSP4 positively regulates p53 by promoting Mdm2 self-ubiquitination. Nat Cell Biol 8:1424–1431

    CAS  PubMed  Google Scholar 

  • Li W, Ding F, Zhang L, Liu Z, Wu Y, Luo A, Wu M, Wang M, Zhan Q, Liu Z (2005) Overexpression of stefin A in human esophageal squamous cell carcinoma cells inhibits tumor cell growth, angiogenesis, invasion, and metastasis. Clin Cancer Res 11:8753–8762

    CAS  PubMed  Google Scholar 

  • List K, Kosa P, Szabo R, Bey AL, Wang CB, Molinolo A, Bugge TH (2009) Epithelial integrity is maintained by a matriptase-dependent proteolytic pathway. Am J Pathol 175:1453–1463

    CAS  PubMed  Google Scholar 

  • Liu Y, Patricelli MP, Cravatt BF (1999) Activity-based protein profiling: the serine hydrolases. Proc Natl Acad Sci U S A 96:14694–14699

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lopez-Otin C, Hunter T (2010) The regulatory crosstalk between kinases and proteases in cancer. Nat Rev Cancer 10:278–292

    CAS  PubMed  Google Scholar 

  • Lopez-Otin C, Overall CM (2002) Protease degradomics: a new challenge for proteomics. Nat Rev Mol Cell Biol 3:509–519

    CAS  PubMed  Google Scholar 

  • Lunkes A, Lindenberg KS, Ben-Haiem L, Weber C, Devys D, Landwehrmeyer GB, Mandel JL, Trottier Y (2002) Proteases acting on mutant huntingtin generate cleaved products that differentially build up cytoplasmic and nuclear inclusions. Mol Cell 10:259–269

    CAS  PubMed  Google Scholar 

  • Luo S, Vacher C, Davies JE, Rubinsztein DC (2005) Cdk5 phosphorylation of huntingtin reduces its cleavage by caspases: implications for mutant huntingtin toxicity. J Cell Biol 169:647–656

    CAS  PubMed  Google Scholar 

  • Magert HJ, Standker L, Kreutzmann P, Zucht HD, Reinecke M, Sommerhoff CP, Fritz H, Forssmann WG (1999) LEKTI, a novel 15-domain type of human serine proteinase inhibitor. J Biol Chem 274:21499–21502

    CAS  PubMed  Google Scholar 

  • Mahrus S, Trinidad JC, Barkan DT, Sali A, Burlingame AL, Wells JA (2008) Global sequencing of proteolytic cleavage sites in apoptosis by specific labeling of protein N termini. Cell 134:866–876

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mann M (2006) Functional and quantitative proteomics using SILAC. Nat Rev Mol Cell Biol 7:952–958

    CAS  PubMed  Google Scholar 

  • Martin L, Latypova X, Terro F (2011) Post-translational modifications of tau protein: implications for Alzheimer’s disease. Neurochem Int 58:458–471

    CAS  PubMed  Google Scholar 

  • McNulty DE, Annan RS (2008) Hydrophilic interaction chromatography reduces the complexity of the phosphoproteome and improves global phosphopeptide isolation and detection. Mol Cell Proteomics 7:971–980

    CAS  PubMed  Google Scholar 

  • Mester G, Hoffmann V, Stevanovic S (2011) Insights into MHC class I antigen processing gained from large-scale analysis of class I ligands. Cell Mol Life Sci 68:1521–1532

    CAS  PubMed  Google Scholar 

  • Millucci L, Ghezzi L, Bernardini G, Santucci A (2010) Conformations and biological activities of amyloid beta peptide 25-35. Curr Protein Pept Sci 11:54–67

    CAS  PubMed  Google Scholar 

  • Miravalle L, Calero M, Takao M, Roher AE, Ghetti B, Vidal R (2005) Amino-terminally truncated Abeta peptide species are the main component of cotton wool plaques. Biochemistry 44:10810–10821

    CAS  PubMed  Google Scholar 

  • Mitsudo K, Jayakumar A, Henderson Y, Frederick MJ, Kang Y, Wang M, El-Naggar AK, Clayman GL (2003) Inhibition of serine proteinases plasmin, trypsin, subtilisin A, cathepsin G, and elastase by LEKTI: a kinetic analysis. Biochemistry 42:3874–3881

    CAS  PubMed  Google Scholar 

  • Miyauchi Y, Yogosawa S, Honda R, Nishida T, Yasuda H (2002) Sumoylation of Mdm2 by protein inhibitor of activated STAT (PIAS) and RanBP2 enzymes. J Biol Chem 277:50131–50136

    CAS  PubMed  Google Scholar 

  • Mommen GP, van de Waterbeemd B, Meiring HD, Kersten G, Heck AJ, de Jong AP (2012) Unbiased selective isolation of protein N-terminal peptides from complex proteome samples using phospho tagging (PTAG) and TiO2-based depletion. Mol Cell Proteomics 11:832–842

    CAS  PubMed  Google Scholar 

  • Mori H, Ishii K, Tomiyama T, Furiya Y, Sahara N, Asano S, Endo N, Shirasawa T, Takio K (1994) Racemization: its biological significance on neuropathogenesis of Alzheimer’s disease. Tohoku J Exp Med 174:251–262

    CAS  PubMed  Google Scholar 

  • Morrissey JH (2012) Polyphosphate: a link between platelets, coagulation and inflammation. Int J Hematol 95:346–352

    CAS  PubMed Central  PubMed  Google Scholar 

  • Murakami K, Uno M, Masuda Y, Shimizu T, Shirasawa T, Irie K (2008) Isomerization and/or racemization at Asp23 of Abeta42 do not increase its aggregative ability, neurotoxicity, and radical productivity in vitro. Biochem Biophys Res Commun 366:745–751

    CAS  PubMed  Google Scholar 

  • Murphy G (2011) Tissue inhibitors of metalloproteinases. Genome Biol 12:233

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mutero A, Fournier D (1992) Post-translational modifications of Drosophila acetylcholinesterase. In vitro mutagenesis and expression in Xenopus oocytes. J Biol Chem 267:1695–1700

    CAS  PubMed  Google Scholar 

  • Nakagawa H, Wakabayashi-Nakao K, Tamura A, Toyoda Y, Koshiba S, Ishikawa T (2009) Disruption of N-linked glycosylation enhances ubiquitin-mediated proteasomal degradation of the human ATP-binding cassette transporter ABCG2. FEBS J 276:7237–7252

    CAS  PubMed  Google Scholar 

  • Nylandsted J, Becker AC, Bunkenborg J, Andersen JS, Dengjel J, Jaattela M (2011) ErbB2-associated changes in the lysosomal proteome. Proteomics 11:2830–2838

    CAS  PubMed  Google Scholar 

  • Ong SE, Mann M (2005) Mass spectrometry-based proteomics turns quantitative. Nat Chem Biol 1:252–262

    CAS  PubMed  Google Scholar 

  • Ong SE, Blagoev B, Kratchmarova I, Kristensen DB, Steen H, Pandey A, Mann M (2002) Stable isotope labeling by amino acids in cell culture, SILAC, as a simple and accurate approach to expression proteomics. Mol Cell Proteomics 1:376–386

    CAS  PubMed  Google Scholar 

  • Opdenakker G, Rudd PM, Ponting CP, Dwek RA (1993) Concepts and principles of glycobiology. FASEB J 7:1330–1337

    CAS  PubMed  Google Scholar 

  • Ott I (2011) Inhibitors of the initiation of coagulation. Br J Clin Pharmacol 72:547–552

    CAS  PubMed  Google Scholar 

  • Overall CM, Blobel CP (2007) In search of partners: linking extracellular proteases to substrates. Nat Rev Mol Cell Biol 8:245–257

    CAS  PubMed  Google Scholar 

  • Overall CM, Dean RA (2006) Degradomics: systems biology of the protease web. Pleiotropic roles of MMPs in cancer. Cancer Metastasis Rev 25:69–75

    PubMed  Google Scholar 

  • Pagano M, Tam SW, Theodoras AM, Beer-Romero P, Del Sal G, Chau V, Yew PR, Draetta GF, Rolfe M (1995) Role of the ubiquitin-proteasome pathway in regulating abundance of the cyclin-dependent kinase inhibitor p27. Science 269:682–685

    CAS  PubMed  Google Scholar 

  • Paulick MG, Bogyo M (2008) Application of activity-based probes to the study of enzymes involved in cancer progression. Curr Opin Genet Dev 18:97–106

    CAS  PubMed Central  PubMed  Google Scholar 

  • Peng J, Schwartz D, Elias JE, Thoreen CC, Cheng D, Marsischky G, Roelofs J, Finley D, Gygi SP (2003) A proteomics approach to understanding protein ubiquitination. Nat Biotechnol 21:921–926

    CAS  PubMed  Google Scholar 

  • Picotti P, Aebersold R, Domon B (2007) The implications of proteolytic background for shotgun proteomics. Mol Cell Proteomics 6:1589–1598

    CAS  PubMed  Google Scholar 

  • Picotti P, Bodenmiller B, Mueller LN, Domon B, Aebersold R (2009) Full dynamic range proteome analysis of S. cerevisiae by targeted proteomics. Cell 138:795–806

    CAS  PubMed Central  PubMed  Google Scholar 

  • Poreba M, Drag M (2010) Current strategies for probing substrate specificity of proteases. Curr Med Chem 17:3968–3995

    CAS  PubMed  Google Scholar 

  • Pratt JM, Petty J, Riba-Garcia I, Robertson DH, Gaskell SJ, Oliver SG, Beynon RJ (2002) Dynamics of protein turnover, a missing dimension in proteomics. Mol Cell Proteomics 1:579–591

    CAS  PubMed  Google Scholar 

  • Price SR, Bailey JL, Wang X, Jurkovitz C, England BK, Ding X, Phillips LS, Mitch WE (1996) Muscle wasting in insulinopenic rats results from activation of the ATP-dependent, ubiquitin-proteasome proteolytic pathway by a mechanism including gene transcription. J Clin Invest 98:1703–1708

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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-TAILS quantitative proteomics. Mol Cell Proteomics 9:894–911

    CAS  PubMed  Google Scholar 

  • Puente XS, Sanchez LM, Overall CM, Lopez-Otin C (2003) Human and mouse proteases: a comparative genomic approach. Nat Rev Genet 4:544–558

    CAS  PubMed  Google Scholar 

  • Puri AW, Bogyo M (2009) Using small molecules to dissect mechanisms of microbial pathogenesis. ACS Chem Biol 4:603–616

    CAS  PubMed Central  PubMed  Google Scholar 

  • Quesada V, Ordonez GR, Sanchez LM, Puente XS, Lopez-Otin C (2009) The Degradome database: mammalian proteases and diseases of proteolysis. Nucleic Acids Res 37:D239–D243

    CAS  PubMed Central  PubMed  Google Scholar 

  • Rawlings ND, Morton FR, Barrett AJ (2006) MEROPS: the peptidase database. Nucleic Acids Res 34:D270–D272

    CAS  PubMed Central  PubMed  Google Scholar 

  • Rawlings ND, Barrett AJ, Bateman A (2010) MEROPS: the peptidase database. Nucleic Acids Res 38:D227–D233

    CAS  PubMed Central  PubMed  Google Scholar 

  • Reiser J, Adair B, Reinheckel T (2010) Specialized roles for cysteine cathepsins in health and disease. J Clin Invest 120:3421–3431

    CAS  PubMed Central  PubMed  Google Scholar 

  • Rock KL, Goldberg AL (1999) Degradation of cell proteins and the generation of MHC class I-presented peptides. Annu Rev Immunol 17:739–779

    CAS  PubMed  Google Scholar 

  • Romao S, Munz C (2011) Autophagy of pathogens alarms the immune system and participates in its effector functions. Swiss Med Wkly 141:w13198

    PubMed  Google Scholar 

  • Ross PL, Huang YN, Marchese JN, Williamson B, Parker K, Hattan S, Khainovski N, Pillai S, Dey S, Daniels S et al (2004) Multiplexed protein quantitation in Saccharomyces cerevisiae using amine-reactive isobaric tagging reagents. Mol Cell Proteomics 3:1154–1169

    CAS  PubMed  Google Scholar 

  • Rubinsztein DC, Carmichael J (2003) Huntington’s disease: molecular basis of neurodegeneration. Expert Rev Mol Med 5:1–21

    PubMed  Google Scholar 

  • Saghatelian A, Jessani N, Joseph A, Humphrey M, Cravatt BF (2004) Activity-based probes for the proteomic profiling of metalloproteases. Proc Natl Acad Sci U S A 101:10000–10005

    CAS  PubMed Central  PubMed  Google Scholar 

  • Saido TC, Iwatsubo T, Mann DM, Shimada H, Ihara Y, Kawashima S (1995) Dominant and differential deposition of distinct beta-amyloid peptide species, A beta N3(pE), in senile plaques. Neuron 14:457–466

    CAS  PubMed  Google Scholar 

  • Saido TC, Yamao-Harigaya W, Iwatsubo T, Kawashima S (1996) Amino- and carboxyl-terminal heterogeneity of beta-amyloid peptides deposited in human brain. Neurosci Lett 215:173–176

    CAS  PubMed  Google Scholar 

  • Sales KU, Masedunskas A, Bey AL, Rasmussen AL, Weigert R, List K, Szabo R, Overbeek PA, Bugge TH (2010) Matriptase initiates activation of epidermal pro-kallikrein and disease onset in a mouse model of Netherton syndrome. Nat Genet 42:676–683

    CAS  PubMed Central  PubMed  Google Scholar 

  • Scheller J, Chalaris A, Garbers C, Rose-John S (2011) ADAM17: a molecular switch to control inflammation and tissue regeneration. Trends Immunol 32:380–387

    CAS  PubMed  Google Scholar 

  • Schilling O, Overall CM (2008) Proteome-derived, database-searchable peptide libraries for identifying protease cleavage sites. Nat Biotechnol 26:685–694

    CAS  PubMed  Google Scholar 

  • Schilling B, Gafni J, Torcassi C, Cong X, Row RH, LaFevre-Bernt MA, Cusack MP, Ratovitski T, Hirschhorn R, Ross CA et al (2006a) Huntingtin phosphorylation sites mapped by mass spectrometry. Modulation of cleavage and toxicity. J Biol Chem 281:23686–23697

    CAS  PubMed  Google Scholar 

  • Schilling S, Lauber T, Schaupp M, Manhart S, Scheel E, Bohm G, Demuth HU (2006b) On the seeding and oligomerization of pGlu-amyloid peptides (in vitro). Biochemistry 45:12393–12399

    CAS  PubMed  Google Scholar 

  • Schilling S, Zeitschel U, Hoffmann T, Heiser U, Francke M, Kehlen A, Holzer M, Hutter-Paier B, Prokesch M, Windisch M et al (2008) Glutaminyl cyclase inhibition attenuates pyroglutamate Abeta and Alzheimer’s disease-like pathology. Nat Med 14:1106–1111

    CAS  PubMed  Google Scholar 

  • Schilling O, Barre O, Huesgen PF, Overall CM (2010) Proteome-wide analysis of protein carboxy termini: C terminomics. Nat Methods 7:508–511

    CAS  PubMed  Google Scholar 

  • Schilling O, auf dem Keller U, Overall CM (2011a) Factor Xa subsite mapping by proteome-derived peptide libraries improved using WebPICS, a resource for proteomic identification of cleavage sites. Biol Chem 392:1031–1037

    CAS  PubMed  Google Scholar 

  • Schilling O, Huesgen PF, Barre O, auf dem Keller U, Overall CM (2011b) Characterization of the prime and non-prime active site specificities of proteases by proteome-derived peptide libraries and tandem mass spectrometry. Nat Protoc 6:111–120

    CAS  PubMed  Google Scholar 

  • Schilling O, Huesgen PF, Barre O, Overall CM (2011c) Identification and relative quantification of native and proteolytically generated protein C-termini from complex proteomes: C-terminome analysis. Methods Mol Biol 781:59–69

    CAS  PubMed  Google Scholar 

  • Schmidt M, Haas W, Crosas B, Santamaria PG, Gygi SP, Walz T, Finley D (2005) The HEAT repeat protein Blm10 regulates the yeast proteasome by capping the core particle. Nat Struct Mol Biol 12:294–303

    CAS  PubMed  Google Scholar 

  • Schwanhausser B, Busse D, Li N, Dittmar G, Schuchhardt J, Wolf J, Chen W, Selbach M (2011) Global quantification of mammalian gene expression control. Nature 473:337–342

    PubMed  Google Scholar 

  • Sergeant N, Bombois S, Ghestem A, Drobecq H, Kostanjevecki V, Missiaen C, Wattez A, David JP, Vanmechelen E, Sergheraert C et al (2003) Truncated beta-amyloid peptide species in pre-clinical Alzheimer’s disease as new targets for the vaccination approach. J Neurochem 85:1581–1591

    CAS  PubMed  Google Scholar 

  • Sevenich L, Schurigt U, Sachse K, Gajda M, Werner F, Muller S, Vasiljeva O, Schwinde A, Klemm N, Deussing J et al (2010) Synergistic antitumor effects of combined cathepsin B and cathepsin Z deficiencies on breast cancer progression and metastasis in mice. Proc Natl Acad Sci U S A 107:2497–2502

    CAS  PubMed Central  PubMed  Google Scholar 

  • Shen A (2010) Allosteric regulation of protease activity by small molecules. Mol Biosyst 6:1431–1443

    CAS  PubMed  Google Scholar 

  • Shimizu T, Watanabe A, Ogawara M, Mori H, Shirasawa T (2000) Isoaspartate formation and neurodegeneration in Alzheimer’s disease. Arch Biochem Biophys 381:225–234

    CAS  PubMed  Google Scholar 

  • Shrikhande GV, Scali ST, da Silva CG, Damrauer SM, Csizmadia E, Putheti P, Matthey M, Arjoon R, Patel R, Siracuse JJ et al (2010) O-glycosylation regulates ubiquitination and degradation of the anti-inflammatory protein A20 to accelerate atherosclerosis in diabetic ApoE-null mice. PLoS One 5:e14240

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sieber SA, Niessen S, Hoover HS, Cravatt BF (2006) Proteomic profiling of metalloprotease activities with cocktails of active-site probes. Nat Chem Biol 2:274–281

    CAS  PubMed Central  PubMed  Google Scholar 

  • Smith R, Johansen HT, Nilsen H, Haugen MH, Pettersen SJ, Maelandsmo GM, Abrahamson M, Solberg R (2012) Intra- and extracellular regulation of activity and processing of legumain by cystatin E/M. Biochimie 94(12):2590–2599

    CAS  PubMed  Google Scholar 

  • Sokol JP, Schiemann WP (2004) Cystatin C antagonizes transforming growth factor beta signaling in normal and cancer cells. Mol Cancer Res 2:183–195

    CAS  PubMed  Google Scholar 

  • Sorimachi H, Ishiura S, Suzuki K (1997) Structure and physiological function of calpains. Biochem J 328(Pt 3):721–732

    CAS  PubMed  Google Scholar 

  • Speers AE, Cravatt BF (2009) Activity-based protein profiling (ABPP) and click chemistry (CC)-ABPP by MudPIT mass spectrometry. Curr Protoc Chem Biol 1:29–41

    PubMed Central  PubMed  Google Scholar 

  • Staes A, Van Damme P, Helsens K, Demol H, Vandekerckhove J, Gevaert K (2008) Improved recovery of proteome-informative, protein N-terminal peptides by combined fractional diagonal chromatography (COFRADIC). Proteomics 8:1362–1370

    CAS  PubMed  Google Scholar 

  • Steffan JS, Agrawal N, Pallos J, Rockabrand E, Trotman LC, Slepko N, Illes K, Lukacsovich T, Zhu YZ, Cattaneo E et al (2004) SUMO modification of Huntingtin and Huntington’s disease pathology. Science 304:100–104

    CAS  PubMed  Google Scholar 

  • Strongin AY, Marmer BL, Grant GA, Goldberg GI (1993) Plasma membrane-dependent activation of the 72-kDa type IV collagenase is prevented by complex formation with TIMP-2. J Biol Chem 268:14033–14039

    CAS  PubMed  Google Scholar 

  • Tanaka K, Waki H, Ido Y, Akita S, Yoshida Y (1988) Protein and polymer analyses up to m/z 100,000 by laser ionization time-of-flight mass spectrometry. Rapid Commun Mass Spectrom 2:151–153

    CAS  Google Scholar 

  • Taylor AK, Wall R (1988) Selective removal of alpha heavy-chain glycosylation sites causes immunoglobulin A degradation and reduced secretion. Mol Cell Biol 8:4197–4203

    CAS  PubMed Central  PubMed  Google Scholar 

  • Taylor RC, Cullen SP, Martin SJ (2008) Apoptosis: controlled demolition at the cellular level. Nat Rev Mol Cell Biol 9:231–241

    CAS  PubMed  Google Scholar 

  • Tekirian TL, Saido TC, Markesbery WR, Russell MJ, Wekstein DR, Patel E, Geddes JW (1998) N-terminal heterogeneity of parenchymal and cerebrovascular Abeta deposits. J Neuropathol Exp Neurol 57:76–94

    CAS  PubMed  Google Scholar 

  • 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 392:961–971

    CAS  PubMed  Google Scholar 

  • Tholen S, Biniossek ML, Gansz M, Ahrens TD, Schlimpert M, Kizhakkedathu JN, Reinheckel T, Schilling O (2013a) Double deficiency of cathepsins B and L results in massive secretome alterations and suggests a degradative cathepsin-MMP axis. Cell Mol Life Sci. doi:10.1007/s00018-013-1406-1

    PubMed  Google Scholar 

  • Tholen S, Biniossek ML, Gansz M, Gomez-Auli A, Bengsch F, Noel A, Kizhakkedathu JN, Boerries M, Busch H, Reinheckel T, Schilling O (2013b) Deletion of cysteine cathepsins B or L yields differential impacts on murine skin proteome and degradome. Mol Cell Proteomics 12:611–625

    CAS  PubMed  Google Scholar 

  • Thornberry NA, Peterson EP, Zhao JJ, Howard AD, Griffin PR, Chapman KT (1994) Inactivation of interleukin-1 beta converting enzyme by peptide (acyloxy)methyl ketones. Biochemistry 33:3934–3940

    CAS  PubMed  Google Scholar 

  • Timmer JC, Enoksson M, Wildfang E, Zhu W, Igarashi Y, Denault JB, Ma Y, Dummitt B, Chang YH, Mast AE et al (2007) Profiling constitutive proteolytic events in vivo. Biochem J 407:41–48

    CAS  PubMed  Google Scholar 

  • Timmer JC, Zhu W, Pop C, Regan T, Snipas SJ, Eroshkin AM, Riedl SJ, Salvesen GS (2009) Structural and kinetic determinants of protease substrates. Nat Struct Mol Biol 16:1101–1108

    CAS  PubMed  Google Scholar 

  • Tolkovsky AM (2009) Mitophagy. Biochim Biophys Acta 1793:1508–1515

    CAS  PubMed  Google Scholar 

  • Tomiyama T, Asano S, Furiya Y, Shirasawa T, Endo N, Mori H (1994) Racemization of Asp23 residue affects the aggregation properties of Alzheimer amyloid beta protein analogues. J Biol Chem 269:10205–10208

    CAS  PubMed  Google Scholar 

  • Tseng A, Inuzuka H, Gao D, Singh A, Wei W (2008) Experimental approaches to investigate the proteasomal degradation pathways involved in regulation of apoptosis. Methods Enzymol 446:205–223

    CAS  PubMed  Google Scholar 

  • Turk B, du Turk SA, Turk V (2012) Protease signalling: the cutting edge. EMBO J 31:1630–1643

    CAS  PubMed  Google Scholar 

  • Van Damme P, Staes A, Bronsoms S, Helsens K, Colaert N, Timmerman E, Aviles FX, Vandekerckhove J, Gevaert K (2010) Complementary positional proteomics for screening substrates of endo- and exoproteases. Nat Methods 7:512–515

    PubMed  Google Scholar 

  • Vande Walle L, Van Damme P, Lamkanfi M, Saelens X, Vandekerckhove J, Gevaert K, Vandenabeele P (2007) Proteome-wide Identification of HtrA2/Omi Substrates. J Proteome Res 6:1006–1015

    CAS  PubMed  Google Scholar 

  • Varki A (1993) Biological roles of oligosaccharides: all of the theories are correct. Glycobiology 3:97–130

    CAS  PubMed  Google Scholar 

  • Vasiljeva O, Papazoglou A, Kruger A, Brodoefel H, Korovin M, Deussing J, Augustin N, Nielsen BS, Almholt K, Bogyo M et al (2006) Tumor cell-derived and macrophage-derived cathepsin B promotes progression and lung metastasis of mammary cancer. Cancer Res 66:5242–5250

    CAS  PubMed  Google Scholar 

  • Vigneswaran N, Wu J, Nagaraj N, James R, Zeeuwen P, Zacharias W (2006) Silencing of cystatin M in metastatic oral cancer cell line MDA-686Ln by siRNA increases cysteine proteinases and legumain activities, cell proliferation and in vitro invasion. Life Sci 78:898–907

    CAS  PubMed  Google Scholar 

  • Wang CC, Bozdech Z, Liu CL, Shipway A, Backes BJ, Harris JL, Bogyo M (2003) Biochemical analysis of the 20 S proteasome of Trypanosoma brucei. J Biol Chem 278:15800–15808

    CAS  PubMed  Google Scholar 

  • Wang B, Sun J, Kitamoto S, Yang M, Grubb A, Chapman HA, Kalluri R, Shi GP (2006) Cathepsin S controls angiogenesis and tumor growth via matrix-derived angiogenic factors. J Biol Chem 281:6020–6029

    CAS  PubMed  Google Scholar 

  • Wang X, Guerrero C, Kaiser P, Huang L (2007) Proteomics of proteasome complexes and ubiquitinated proteins. Expert Rev Proteomics 4:649–665

    CAS  PubMed  Google Scholar 

  • Weissman AM (2001) Themes and variations on ubiquitylation. Nat Rev Mol Cell Biol 2:169–178

    CAS  PubMed  Google Scholar 

  • Wellington CL, Singaraja R, Ellerby L, Savill J, Roy S, Leavitt B, Cattaneo E, Hackam A, Sharp A, Thornberry N et al (2000) Inhibiting caspase cleavage of huntingtin reduces toxicity and aggregate formation in neuronal and nonneuronal cells. J Biol Chem 275:19831–19838

    CAS  PubMed  Google Scholar 

  • Wellington CL, Ellerby LM, Gutekunst CA, Rogers D, Warby S, Graham RK, Loubser O, van Raamsdonk J, Singaraja R, Yang YZ et al (2002) Caspase cleavage of mutant huntingtin precedes neurodegeneration in Huntington’s disease. J Neurosci 22:7862–7872

    CAS  PubMed  Google Scholar 

  • Wickner S, Maurizi MR, Gottesman S (1999) Posttranslational quality control: folding, refolding, and degrading proteins. Science 286:1888–1893

    CAS  PubMed  Google Scholar 

  • Wild P, Farhan H, McEwan DG, Wagner S, Rogov VV, Brady NR, Richter B, Korac J, Waidmann O, Choudhary C et al (2011) Phosphorylation of the autophagy receptor optineurin restricts Salmonella growth. Science 333:228–233

    CAS  PubMed Central  PubMed  Google Scholar 

  • Williams EB, Krishnaswamy S, Mann KG (1989) Zymogen/enzyme discrimination using peptide chloromethyl ketones. J Biol Chem 264:7536–7545

    CAS  PubMed  Google Scholar 

  • Witze ES, Old WM, Resing KA, Ahn NG (2007) Mapping protein post-translational modifications with mass spectrometry. Nat Methods 4:798–806

    CAS  PubMed  Google Scholar 

  • Wyss DF, Choi JS, Li J, Knoppers MH, Willis KJ, Arulanandam AR, Smolyar A, Reinherz EL, Wagner G (1995) Conformation and function of the N-linked glycan in the adhesion domain of human CD2. Science 269:1273–1278

    CAS  PubMed  Google Scholar 

  • Xu G, Shin SB, Jaffrey SR (2009a) Global profiling of protease cleavage sites by chemoselective labeling of protein N-termini. Proc Natl Acad Sci U S A 106:19310–19315

    CAS  PubMed Central  PubMed  Google Scholar 

  • Xu P, Duong DM, Seyfried NT, Cheng D, Xie Y, Robert J, Rush J, Hochstrasser M, Finley D, Peng J (2009b) Quantitative proteomics reveals the function of unconventional ubiquitin chains in proteasomal degradation. Cell 137:133–145

    CAS  PubMed Central  PubMed  Google Scholar 

  • Xu G, Paige JS, Jaffrey SR (2010) Global analysis of lysine ubiquitination by ubiquitin remnant immunoaffinity profiling. Nat Biotechnol 28:868–873

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yang Z, Klionsky DJ (2010) Mammalian autophagy: core molecular machinery and signaling regulation. Curr Opin Cell Biol 22:124–131

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yong VW, Krekoski CA, Forsyth PA, Bell R, Edwards DR (1998) Matrix metalloproteinases and diseases of the CNS. Trends Neurosci 21:75–80

    CAS  PubMed  Google Scholar 

  • Zeeuwen PL, van Vlijmen-Willems IM, Cheng T, Rodijk-Olthuis D, Hitomi K, Hara-Nishimura I, John S, Smyth N, Reinheckel T, Hendriks WJ et al (2010) The cystatin M/E-cathepsin L balance is essential for tissue homeostasis in epidermis, hair follicles, and cornea. FASEB J 24:3744–3755

    CAS  PubMed  Google Scholar 

  • Zhang J, Shridhar R, Dai Q, Song J, Barlow SC, Yin L, Sloane BF, Miller FR, Meschonat C, Li BD et al (2004) Cystatin m: a novel candidate tumor suppressor gene for breast cancer. Cancer Res 64:6957–6964

    CAS  PubMed  Google Scholar 

  • Zimmermann AC, Zarei M, Eiselein S, Dengjel J (2010) Quantitative proteomics for the analysis of spatio-temporal protein dynamics during autophagy. Autophagy 6:1009–1016

    CAS  PubMed  Google Scholar 

  • Zogg T, Brandstetter H (2009) Activation mechanisms of coagulation factor IX. Biol Chem 390:391–400

    PubMed  Google Scholar 

Download references

Acknowledgements

O.S. is supported by the Deutsche Forschungsgemeinschaft (DFG, SCHI 871/2 (Emmy-Noether) and SCHI 871/5), a starting grant of the European Research Council (Programme “Ideas”—Call identifier: ERC-2011-StG 282111-ProteaSys), and the Excellence Initiative of the German Federal and State Governments (EXC 294, BIOSS). J.D. is supported by the Excellence Initiative of the German Federal and State Governments through Freiburg Institute for Advanced Studies (FRIAS), School of Life Sciences—LifeNet and the Center for Biological Signalling Studies (BIOSS), by grants DE 1757/2-1 from the German Research Foundation, DFG, and through GerontoSys II—NephAge (031 5896 A) from the German Ministry for Education and Research, BMBF.

Author information

Authors and Affiliations

  1. Institute for Molecular Medicine and Cell Research, University of Freiburg, 79104, Freiburg, Germany

    Stefan Tholen, Maria Magdalena Koczorowska & Zon Weng Lai

  2. Faculty of Biology, University of Freiburg, D-79104, Freiburg, Germany

    Stefan Tholen

  3. Freiburg Institute for Advanced Studies (FRIAS), School of Life Science-LifeNet, University of Freiburg, 79104, Freiburg, Germany

    Joern Dengjel

  4. ZBSA Center for Biological Systems Analysis, University of Freiburg, 79104, Freiburg, Germany

    Joern Dengjel

  5. BIOSS Centre for Biological Signaling Studies, University of Freiburg, 79104, Freiburg, Germany

    Joern Dengjel

  6. Institute for Molecular Medicine and Cell Research, University of Freiburg, D-79104, Freiburg, Germany

    Oliver Schilling

  7. BIOSS Centre for Biological Signaling Studies, University of Freiburg, D-79104, Freiburg, Germany

    Oliver Schilling

Authors
  1. Stefan Tholen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maria Magdalena Koczorowska
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zon Weng Lai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Joern Dengjel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Oliver Schilling
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Oliver Schilling .

Editor information

Editors and Affiliations

  1. SCHOOL OF ENGINEERING AND SCIENCE, JACOBS UNIVERSITY BREMEN, Bremen, Germany

    Klaudia Brix

  2. Institute of Zoology, Johannes Gutenberg University Mainz, Mainz, Germany

    Walter Stöcker

Rights and permissions

Reprints and Permissions

Copyright information

© 2013 Springer-Verlag Wien

About this chapter

Cite this chapter

Tholen, S., Koczorowska, M.M., Lai, Z.W., Dengjel, J., Schilling, O. (2013). Limited and Degradative Proteolysis in the Context of Posttranslational Regulatory Networks: Current Technical and Conceptional Advances. In: Brix, K., Stöcker, W. (eds) Proteases: Structure and Function. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0885-7_5

Download citation