Research Unit
Degradomics
Prof. Dr. Christoph Becker-Pauly
Tel. +49 431 880-7118
Christoph Becker-Pauly is spokesperson of the DFG-funded Research Training Group ReMPro and has published over 100 research papers on the structure and function of proteolytic enzymes in health and disease. Proteases are considered central nodes in the regulation of the immune system, in neurodegeneration, and in cancer. Among the nearly 600 human proteases, his group is particularly interested in the characterization of metalloproteases, especially meprins, ADAM10/17, and MMPs. Using N-terminomics, cell culture, and mouse models, his group has discovered important biological functions of these enzymes in mucosal homeostasis, Alzheimer's disease, tumor progression, and systemic and local inflammatory diseases.
Publications
By Year
Other
2026
J Invest Dermatol. 2026 Feb 10:S0022-202X(26)00084-9. doi: 10.1016/j.jid.2026.01.034. Online ahead of print.
Meprin β elevates hippocampal soluble Aβ in the APP/V717I mouse model.
Exp Neurol. 2026 Mar;397:115600. doi: 10.1016/j.expneurol.2025.115600. Epub 2025 Dec 19.
2025
Type I interferon limits interleukin-6 signaling in SLE through shedding interleukin-6 receptors].
Rheumatology (Oxford). 2025 Jul 9:keaf281. doi: 10.1093/rheumatology/keaf281.
Meprin β Modulates Brevican Proteolysis Impairing Neural Plasticity and Memory Formation.
FASEB J. 2025 May 31;39(10):e70616. doi: 10.1096/fj.202500017R.
HYTANE-Identified Latrophilin-3 Cleavage by Meprin β Leads to Loss of the Interaction Domains.
J Proteome Res. 2025 Apr 4;24(4):1832-1844. doi: 10.1021/acs.jproteome.4c00912. Epub 2025 Mar 26.
Targeted approach to determine the impact of cancer-associated protease variants.
Bickenbach K, David N, Koudelka T, Joos C, Scharfenberg F, Rüffer M, Armbrust F, Georgiadis D, Beau F, Stahmer L, Rahn S, Tholey A, Pietrzik C, Becker-Pauly C.
Sci Adv. 2025 Feb 14;11(7):eadp5958.
2024
Cleavage site-directed antibodies reveal the prion protein in humans is shed by ADAM10 at Y226 and associates with misfolded protein deposits in neurodegenerative diseases.
Song F, Kovac V, Mohammadi B, Littau JL, Scharfenberg F, Matamoros Angles A, Vanni I, Shafiq M, Orge L, Galliciotti G, Djakkani S, Linsenmeier L, Černilec M, Hartman K, Jung S, Tatzelt J, Neumann JE, Damme M, Tschirner SK, Lichtenthaler SF, Ricklefs FL, Sauvigny T, Schmitz M, Zerr I, Puig B, Tolosa E, Ferrer I, Magnus T, Rupnik MS, Sepulveda-Falla D, Matschke J, Šmid LM, Bresjanac M, Andreoletti O, Krasemann S, Foliaki ST, Nonno R, Becker-Pauly C, Monzo C, Crozet C, Haigh CL, Glatzel M, Curin Serbec V, Altmeppen HC.
Acta Neuropathol. 2024 Jul 9;148(1):2.
A novel mouse model for N-terminal truncated Aβ2-x generation through meprin β overexpression in astrocytes.
Armbrust F, Bickenbach K, Altmeppen H, Foggetti A, Winkelmann A, Wulff P, Glatzel M, Pietrzik CU, Becker-Pauly C.
Cell Mol Life Sci. 2024 Mar 13;81(1):139.
2023
Identification of PCPE-2 as the endogenous specific inhibitor of human BMP-1/tolloid-like proteinases.
Vadon-Le Goff S, Tessier A, Napoli M, Dieryckx C, Bauer J, Dussoyer M, Lagoutte P, Peyronnel C, Essayan L, Kleiser S, Tueni N, Bettler E, Mariano N, Errazuriz-Cerda E, Fruchart Gaillard C, Ruggiero F, Becker-Pauly C, Allain JM, Bruckner-Tuderman L, Nyström A, Moali C.
Nat Commun. 2023 Dec 4;14(1):8020.
Proteolysis of CD44 at the cell surface controls a downstream protease network.
Wöhner B, Li W, Hey S, Drobny A, Werny L, Becker-Pauly C, Lucius R, Zunke F, Linder S, Arnold P.
Front Mol Biosci. 2023 Feb 17;10:1026810.
The putative pleiotropic functions of meprin β in gastric cancer.
Siemsen W, Halske C, Behrens HM, Krüger S, Becker-Pauly C, Röcken C.
Gastric Cancer. 2023 Jul;26(4):542-552.
Proteolytic processing of galectin-3 by meprin metalloproteases is crucial for host-microbiome homeostasis.
Bülck C, Nyström EEL, Koudelka T, Mannbar-Frahm M, Andresen G, Radhouani M, Tran F, Scharfenberg F, Schrell F, Armbrust F, Dahlke E, Zhao B, Vervaeke A, Theilig F, Rosenstiel P, Starkl P, Rosshart SP, Fickenscher H, Tholey A, Hansson GC, Becker-Pauly C.
Sci Adv. 2023 Mar 31;9(13):eadf4055.
2022
Zymogenic latency in an ∼250-million-year-old astacin metallopeptidase.
Guevara T, Rodríguez-Banqueri A, Stöcker W, Becker-Pauly C, Gomis-Rüth FX.
Acta Crystallogr D Struct Biol. 2022 Nov 1;78(Pt 11):1347-1357.
PCSK9 acts as a key regulator of Aβ clearance across the blood-brain barrier.
Mazura AD, Ohler A, Storck SE, Kurtyka M, Scharfenberg F, Weggen S, Becker-Pauly C, Pietrzik CU.
Cell Mol Life Sci. 2022 Mar 27;79(4):212.
Meprin β knockout reduces brain Aβ levels and rescues learning and memory impairments in the APP/lon mouse model for Alzheimer's disease.
Marengo L, Armbrust F, Schoenherr C, Storck SE, Schmitt U, Zampar S, Wirths O, Altmeppen H, Glatzel M, Kaether C, Weggen S, Becker-Pauly C, Pietrzik CU.
Cell Mol Life Sci. 2022 Mar 2;79(3):168.
Meprin and ADAM proteases as triggers of systemic inflammation in sepsis.
Rahn S, Becker-Pauly C.
FEBS Lett. 2022 Mar;596(5):534-556. Review.
Identifying causal serum protein-cardiometabolic trait relationships using whole genome sequencing.
Png G, Gerlini R, Hatzikotoulas K, Barysenka A, Rayner NW, Klarić L, Rathkolb B, Aguilar-Pimentel JA, Rozman J, Fuchs H, Gailus-Durner V, Tsafantakis E, Karaleftheri M, Dedoussis G, Pietrzik C, Wilson JF, Angelis MH, Becker-Pauly C, Gilly A, Zeggini E.
Hum Mol Genet. 2022 Mar;596(5):534-556.
MT1-MMP and ADAM10/17 exhibit a remarkable overlap of shedding properties.
Werny L, Grogro A, Bickenbach K, Bülck C, Armbrust F, Koudelka T, Pathak K, Scharfenberg F, Sammel M, Sheikhouny F, Tholey A, Linder S, Becker-Pauly C.
FEBS J. 2022 Mar;596(5):534-556.
Inhibition of ADAM17 impairs endothelial cell necroptosis and blocks metastasis.
Bolik J, Krause F, Stevanovic M, Gandraß M, Thomsen I, Schacht SS, Rieser E, Müller M, Schumacher N, Fritsch J, Wichert R, Galun E, Bergmann J, Röder C, Schafmayer C, Egberts JH, Becker-Pauly C, Saftig P, Lucius R, Schneider-Brachert W, Barikbin R, Adam D, Voss M, Hitzl W, Krüger A, Strilic B, Sagi I, Walczak H, Rose-John S, Schmidt-Arras D.
J Exp Med. 2022 Jan 3;219(1):e20201039.
2021
Identification of Mep1a as a susceptibility gene for atherosclerosis in mice.
Grainger AT, Pilar N, Li J, Chen MH, Abramson AM, Becker-Pauly C, Shi W.
Genetics. 2021 Dec 10;219(4):iyab160.
Corrigendum to "Syndecan-1 shedding by meprin β impairs keratinocyte adhesion and differentiation in hyperkeratosis".
Peters F, Rahn S, Mengel M, Scharfenberg F, Otte A, Koudelka T, Wagner EF, Wunderlich FT, Haase M, Naumann R, Tholey A, Becker-Pauly C.
Matrix Biol. 2021 Nov 2:S0945-053X(21)00096-2.
The Swedish dilemma - the almost exclusive use of APPswe-based mouse models impedes adequate evaluation of alternative β-secretases.
Armbrust F, Bickenbach K, Marengo L, Pietrzik C, Becker-Pauly C.
Biochim Biophys Acta Mol Cell Res. 2021 Oct 23:119164.
Characterization of the Cancer-Associated Meprin Βeta Variants G45R and G89R.
Gellrich A, Scharfenberg F, Peters F, Sammel M, Helm O, Armbrust F, Schmidt F, Lokau J, Garbers C, Sebens S, Arnold P, Becker-Pauly C.
Front Mol Biosci. 2021 Oct 6;8:702341.
Regulation of meprin metalloproteases in mucosal homeostasis.
Werny L, Colmorgen C, Becker-Pauly C.
Biochim Biophys Acta Mol Cell Res. 2021 Oct 6;1869(1):119158.
Syndecan-1 shedding by meprin β impairs keratinocyte adhesion and differentiation in hyperkeratosis.
Peters F, Rahn S, Mengel M, Scharfenberg F, Otte A, Koudelka T, Wagner EF, Wunderlich FT, Haase M, Naumann R, Tholey A, Becker-Pauly C.
Matrix Biol. 2021 Aug;102:37-69.
Phosphorylation of meprin β controls its cell surface abundance and subsequently diminishes ectodomain shedding.
Armbrust F, Bickenbach K, Koudelka T, Tholey A, Pietrzik C, Becker-Pauly C.
FASEB J. 2021 Jul;35(7):e21677.
Distinct contributions of meprins to skin regeneration after injury - Meprin α a physiological processer of pro-collagen VII.
Kruppa D, Peters F, Bornert O, Maler MD, Martin SF, Becker-Pauly C, Nyström A.
Matrix Biol Plus. 2021 May 13;11:100065.
Cell Surface Processing of CD109 by Meprin β Leads to the Release of Soluble Fragments and Reduced Expression on Extracellular Vesicles.
Lückstädt W, Bub S, Koudelka T, Pavlenko E, Peters F, Somasundaram P, Becker-Pauly C, Lucius R, Zunke F, Arnold P.
Front Cell Dev Biol. 2021 Mar 2;9:622390.
Discovery and Optimization of Selective Inhibitors of Meprin α (Part II).
Wang C, Diez J, Park H, Spicer TP, Scampavia LD, Becker-Pauly C, Fields GB, Minond D, Bannister TD.
Pharmaceuticals (Basel). 2021 Feb 27;14(3):197.
Discovery and Optimization of Selective Inhibitors of Meprin α (Part I).
Hou S, Diez J, Wang C, Becker-Pauly C, Fields GB, Bannister T, Spicer TP, Scampavia LD, Minond D.
Pharmaceuticals (Basel). 2021 Feb 28;14(3):203.
Meprin β: A novel regulator of blood-brain barrier integrity.
Gindorf M, Storck SE, Ohler A, Scharfenberg F, Becker-Pauly C, Pietrzik CU.
J Cereb Blood Flow Metab. 2021 Jan;41(1):31-44.
2020
Cathepsin S provokes interleukin-6 (IL-6) trans-signaling through cleavage of the IL-6 receptor in vitro.
Flynn CM, Garbers Y, Düsterhöft S, Wichert R, Lokau J, Lehmann CHK, Dudziak D, Schröder B, Becker-Pauly C, Rose-John S, Aparicio-Siegmund S, Garbers C.
Sci Rep. 2020 Dec 10;10(1):21612.
IL-6 Trans-Signaling in the Brain Influences the Metabolic Phenotype of the 3xTg-AD Mouse Model of Alzheimer's Disease.
Escrig A, Molinero A, Méndez B, Giralt M, Comes G, Sanchis P, Fernández-Gayol O, Giménez-Llort L, Becker-Pauly C, Rose-John S, Hidalgo J.
Cells. 2020 Jul 2;9(7):1605.
Joint Reconstituted Signaling of the IL-6 Receptor via Extracellular Vesicles.
Arnold P, Lückstädt W, Li W, Boll I, Lokau J, Garbers C, Lucius R, Rose-John S, Becker-Pauly C.
Cells. 2020 May 24;9(5):1307.
Meprin β cleaves TREM2 and controls its phagocytic activity on macrophages.
Berner DK, Wessolowski L, Armbrust F, Schneppenheim J, Schlepckow K, Koudelka T, Scharfenberg F, Lucius R, Tholey A, Kleinberger G, Haass C, Arnold P, Becker-Pauly C.
FASEB J. 2020 May;34(5):6675-6687
Loss of ADAMTS19 causes progressive non-syndromic heart valve disease.
Wünnemann F, Ta-Shma A, Preuss C, Leclerc S, van Vliet PP, Oneglia A, Thibeault M, Nordquist E, Lincoln J, Scharfenberg F, Becker-Pauly C, Hofmann P, Hoff K, Audain E, Kramer HH, Makalowski W, Nir A, Gerety SS, Hurles M, Comes J, Fournier A, Osinska H, Robins J, Pucéat M; MIBAVA Leducq Consortium principal investigators, Elpeleg O, Hitz MP, Andelfinger G.
Nat Genet. 2020 Jan;52(1):40-47
Degradome of soluble ADAM10 and ADAM17 metalloproteases.
Scharfenberg F, Helbig A, Sammel M, Benzel J, Schlomann U, Peters F, Wichert R, Bettendorff M, Schmidt-Arras D, Rose-John S, Moali C, Lichtenthaler SF, Pietrzik CU, Bartsch JW, Tholey A, Becker-Pauly C.
Cell Mol Life Sci. 2020 Jan;77(2):331-350
2019
IL-6 trans-signaling in the brain influences the behavioral and physio-pathological phenotype of the Tg2576 and 3xTgAD mouse models of Alzheimer's disease.
Escrig A, Canal C, Sanchis P, Fernández-Gayol O, Montilla A, Comes G, Molinero A, Giralt M, Giménez-Llort L, Becker-Pauly C, Rose-John S, Hidalgo J.
Brain Behav Immun. 2019 Nov;82:145-159
Meprin β induces activities of A disintegrin and metalloproteinases 9, 10, and 17 by specific prodomain cleavage.
Wichert R, Scharfenberg F, Colmorgen C, Koudelka T, Schwarz J, Wetzel S, Potempa B, Potempa J, Bartsch JW, Sagi I, Tholey A, Saftig P, Rose-John S, Becker-Pauly C.
FASEB J. 2019 Nov;33(11):11925-11940
Role of meprin metalloproteases in metastasis and tumor microenvironment.
Peters F, Becker-Pauly C.
Cancer Metastasis Rev. 2019 Sep;38(3):347-356. Review.
Regulation of the alternative β-secretase meprin β by ADAM-mediated shedding.
Scharfenberg F, Armbrust F, Marengo L, Pietrzik C, Becker-Pauly C.
Cell Mol Life Sci. 2019 Aug;76(16):3193-3206. Review.
Differences in Shedding of the Interleukin-11 Receptor by the Proteases ADAM9, ADAM10, ADAM17, Meprin α, Meprin β and MT1-MMP.
Sammel M, Peters F, Lokau J, Scharfenberg F, Werny L, Linder S, Garbers C, Rose-John S, Becker-Pauly C.
Int J Mol Sci. 2019 Jul 26;20(15)
Tethering soluble meprin α in an enzyme complex to the cell surface affects IBD-associated genes.
Peters F, Scharfenberg F, Colmorgen C, Armbrust F, Wichert R, Arnold P, Potempa B, Potempa J, Pietrzik CU, Häsler R, Rosenstiel P, Becker-Pauly C.
FASEB J. 2019 Jun;33(6):7490-7504
The cancer associated meprin β variant p.G32R provides an additional activation site and promotes cancer cell invasion.
Schäffler H, Li W, Helm O, Krüger S, Böger C, Peters F, Röcken C, Sebens S, Lucius R, Becker-Pauly C, Arnold P.
J Cell Sci. 2019 May 31;132(11)
Propeptide glycosylation and galectin-3 binding decrease proteolytic activation of human proMMP-9/progelatinase B.
Boon L, Ugarte-Berzal E, Martens E, Vandooren J, Rybakin V, Colau D, Gordon-Alonso M, van der Bruggen P, Stöcker W, Becker-Pauly C, Witters P, Morava-Kozics E, Jaeken J, Proost P, Opdenakker G.
FEBS J. 2019 Mar;286(5):930-945
The metalloprotease ADAMTS4 generates N-truncated Aβ4-x species and marks oligodendrocytes as a source of amyloidogenic peptides in Alzheimer's disease.
Walter S, Jumpertz T, Hüttenrauch M, Ogorek I, Gerber H, Storck SE, Zampar S, Dimitrov M, Lehmann S, Lepka K, Berndt C, Wiltfang J, Becker-Pauly C, Beher D, Pietrzik CU, Fraering PC, Wirths O, Weggen S.
Acta Neuropathol. 2019 Feb;137(2):239-257
Mammalian plasma fetuin-B is a selective inhibitor of ovastacin and meprin metalloproteinases.
Karmilin K, Schmitz C, Kuske M, Körschgen H, Olf M, Meyer K, Hildebrand A, Felten M, Fridrich S, Yiallouros I, Becker-Pauly C, Weiskirchen R, Jahnen-Dechent W, Floehr J, Stöcker W.
Sci Rep. 2019 Jan 24;9(1):546
2018
Inhibitors of BMP-1/tolloid-like proteinases: efficacy, selectivity and cellular toxicity.
Talantikite M, Lécorché P, Beau F, Damour O, Becker-Pauly C, Ho WB, Dive V, Vadon-Le Goff S, Moali C.
FEBS Open Bio. 2018 Nov 12;8(12):2011-2021
Docking of Meprin α to Heparan Sulphate Protects the Endothelium from Inflammatory Cell Extravasation.
Biasin V, Wygrecka M, Bärnthaler T, Jandl K, Jain PP, Bálint Z, Kovacs G, Leitinger G, Kolb-Lenz D, Kornmueller K, Peters F, Sinn K, Klepetko W, Heinemann A, Olschewski A, Becker-Pauly C, Kwapiszewska G.
Thromb Haemost. 2018 Oct;118(10):1790-1802
ADAM17 is required for EGF-R-induced intestinal tumors via IL-6 trans-signaling.
Schmidt S, Schumacher N, Schwarz J, Tangermann S, Kenner L, Schlederer M, Sibilia M, Linder M, Altendorf-Hofmann A, Knösel T, Gruber ES, Oberhuber G, Bolik J, Rehman A, Sinha A, Lokau J, Arnold P, Cabron AS, Zunke F, Becker-Pauly C, Preaudet A, Nguyen P, Huynh J, Afshar-Sterle S, Chand AL, Westermann J, Dempsey PJ, Garbers C, Schmidt-Arras D, Rosenstiel P, Putoczki T, Ernst M, Rose-John S.
J Exp Med. 2018 Apr 2;215(4):1205-1225
2017
Mucus Detachment by Host Metalloprotease Meprin β Requires Shedding of Its Inactive Pro-form, which Is Abrogated by the Pathogenic Protease RgpB.
Wichert R, Ermund A, Schmidt S, Schweinlin M, Ksiazek M, Arnold P, Knittler K, Wilkens F, Potempa B, Rabe B, Stirnberg M, Lucius R, Bartsch JW, Nikolaus S, Falk-Paulsen M, Rosenstiel P, Metzger M, Rose-John S, Potempa J, Hansson GC, Dempsey PJ, Becker-Pauly C.
Cell Rep. 2017 Nov 21;21(8):2090-2103
Meprin metalloproteases: Molecular regulation and function in inflammation and fibrosis.
Arnold P, Otte A, Becker-Pauly C.
Biochim Biophys Acta Mol Cell Res. 2017 Nov;1864(11 Pt B):2096-2104. Review.
Cancer-associated mutations in the canonical cleavage site do not influence CD99 shedding by the metalloprotease meprin β but alter cell migration in vitro.
Bedau T, Schumacher N, Peters F, Prox J, Arnold P, Koudelka T, Helm O, Schmidt F, Rabe B, Jentzsch M, Rosenstiel P, Sebens S, Tholey A, Rose-John S, Becker-Pauly C.
Oncotarget. 2017 Jul 4;8(33):54873-54888
Meprin β and BMP-1 are differentially regulated by CaCl2.
Schneppenheim J, Scharfenberg F, Lucius R, Becker-Pauly C, Arnold P.
Cell Calcium. 2017 Jul;65:8-13
Meprin Metalloproteases Generate Biologically Active Soluble Interleukin-6 Receptor to Induce Trans-Signaling.
Arnold P, Boll I, Rothaug M, Schumacher N, Schmidt F, Wichert R, Schneppenheim J, Lokau J, Pickhinke U, Koudelka T, Tholey A, Rabe B, Scheller J, Lucius R, Garbers C, Rose-John S, Becker-Pauly C.
Sci Rep. 2017 Mar 9;7:44053
Ectodomain shedding of CD99 within highly conserved regions is mediated by the metalloprotease meprin β and promotes transendothelial cell migration.
Bedau T, Peters F, Prox J, Arnold P, Schmidt F, Finkernagel M, Köllmann S, Wichert R, Otte A, Ohler A, Stirnberg M, Lucius R, Koudelka T, Tholey A, Biasin V, Pietrzik CU, Kwapiszewska G, Becker-Pauly C.
FASEB J. 2017 Mar;31(3):1226-1237
Deficiency of the DSPP-cleaving enzymes meprin α and meprin β does not result in dentin malformation in mice.
Arnold P, Koopmann L, Peters F, Birkenfeld , Goff SV, Damm T, Qin C, Moali C, Lucius R, Becker-Pauly C.
Cell Tissue Res. 2017 Feb;367(2):351-358
The Metalloprotease Meprin β Is an Alternative β-Secretase of APP.
Becker-Pauly C, Pietrzik CU.
Front Mol Neurosci. 2017 Jan 5;9:159. Review.
Proteolytic Origin of the Soluble Human IL-6R In Vivo and a Decisive Role of N-Glycosylation.
Riethmueller S, Somasundaram P, Ehlers JC, Hung CW, Flynn CM, Lokau J, Agthe M, Düsterhöft S, Zhu Y, Grötzinger J, Lorenzen I, Koudelka T, Yamamoto K, Pickhinke U, Wichert R, Becker-Pauly C, Rädisch M, Albrecht A, Hessefort M, Stahnke D, Unverzagt C, Rose-John S, Tholey A, Garbers C.
Front Mol Neurosci. 2017 Jan 5;9:159
Meprin β contributes to collagen deposition in lung fibrosis.
Biasin V, Wygrecka M, Marsh LM, Becker-Pauly C, Brcic L, Ghanim B, Klepetko W, Olschewski A, Kwapiszewska G.
Sci Rep. 2017 Jan 6;7:39969
Metalloproteinase meprin α regulates migration and invasion of human hepatocarcinoma cells and is a mediator of the oncoprotein Reptin.
Breig O, Yates M, Neaud V, Couchy G, Grigoletto A, Lucchesi C, Prox J, Zucman-Rossi J, Becker-Pauly C, Rosenbaum J.
Oncotarget. 2017 Jan 31;8(5):7839-7851
2016
Discovery of an enzyme and substrate selective inhibitor of ADAM10 using an exosite-binding glycosylated substrate.
Madoux F, Dreymuller D, Pettiloud JP, Santos R, Becker-Pauly C, Ludwig A, Fields GB, Bannister T, Spicer TP, Cudic M, Scampavia LD, Minond D.
Sci Rep. 2016 Dec 5;6(1):11
Novel Potent Proline-Based Metalloproteinase Inhibitors: Design, (Radio)Synthesis, and First in Vivo Evaluation as Radiotracers for Positron Emission Tomography.
Kalinin DV, Wagner S, Riemann B, Hermann S, Schmidt F, Becker-Pauly C, Rose-John S, Schäfers M, Holl R.
J Med Chem. 2016 Oct 27;59(20):9541-9559
Tetraspanin 8 is an interactor of the metalloprotease meprin β within tetraspanin-enriched microdomains.
Schmidt F, Müller M, Prox J, Arnold P, Schönherr C, Tredup C, Minder P, Ebsen H, Janssen O, Annaert W, Pietrzik C, Schmidt-Arras D, Sterchi EE, Becker-Pauly C.
Biol Chem. 2016 Sep 1;397(9):857-69
The intact Kunitz domain protects the amyloid precursor protein from being processed by matriptase-2.
Beckmann AM, Glebov K, Walter J, Merkel O, Mangold M, Schmidt F, Becker-Pauly C, Gütschow M, Stirnberg M.
Biol Chem. 2016 Aug 1;397(8):777-90
Mice are not Men: ADAM30 Findings Emphasize a Broader Look Towards Murine Alzheimer's Disease Models.
Becker-Pauly C, Pietrzik CU.
EBioMedicine. 2016 Jul;9:19-20
The role of interleukin-6 signaling in nervous tissue.
Rothaug M, Becker-Pauly C, Rose-John S.
Biochim Biophys Acta. 2016 Jun;1863(6 Pt A):1218-27. Review.
Development and Validation of a Small Single-domain Antibody That Effectively Inhibits Matrix Metalloproteinase 8.
Demeestere D, Dejonckheere E, Steeland S, Hulpiau P, Haustraete J, Devoogdt N, Wichert R, Becker-Pauly C, Van Wonterghem E, Dewaele S, Van Imschoot G, Aerts J, Arckens L, Saeys Y, Libert C, Vandenbroucke RE.
Mol Ther. 2016 May;24(5):890-902
Human and murine Interleukin 23 receptors are novel substrates for a disintegrin and metalloproteases ADAM10 and ADAM17.
Franke M, Schröder J, Monhasery N, Ackfeld T, Hummel TM, Rabe B, Garbers C, Becker-Pauly C, Floss DM, Scheller J.
J Biol Chem. 2016 May 13;291(20):10551-61
Determination of Cleavage Site of Reelin between Its Sixth and Seventh Repeat and Contribution of Meprin Metalloproteases to the Cleavage.
Sato Y, Kobayashi D, Kohno T, Kidani Y, Prox J, Becker-Pauly C, Hattori M.
J Biochem. 2016 Mar;159(3):305-12
Generation of aggregation prone N-terminally truncated amyloid β peptides by meprin β depends on the sequence specificity at the cleavage site.
Schönherr C, Bien J, Isbert S, Wichert R, Prox J, Altmeppen H, Kumar S, Walter J, Lichtenthaler SF, Weggen S, Glatzel M, Becker-Pauly C, Pietrzik CU.
Mol Neurodegener. 2016 Feb 19;11:19
2015
Enhanced Peptide Stability Against Protease Digestion Induced by Intrinsic Factor Binding of a Vitamin B12 Conjugate of Exendin-4.
Bonaccorso RL, Chepurny OG, Becker-Pauly C, Holz GG, Doyle RP.
Mol Pharm. 2015 Sep 8;12(9):3502-6
Metalloprotease meprin β is activated by transmembrane serine protease matriptase-2 at the cell surface thereby enhancing APP shedding.
Jäckle F, Schmidt F, Wichert R, Arnold P, Prox J, Mangold M, Ohler A, Pietrzik CU, Koudelka T, Tholey A, Gütschow M, Stirnberg M, Becker-Pauly C.
Biochem J. 2015 Aug 15;470(1):91-103
Calcium negatively regulates meprin β activity and attenuates substrate cleavage.
Arnold P, Schmidt F, Prox J, Zunke F, Pietrzik C, Lucius R, Becker-Pauly C.
FASEB J. 2015 Aug;29(8):3549-57
Meprin α and meprin β: Procollagen proteinases in health and disease.
Prox J, Arnold P, Becker-Pauly C.
Matrix Biol. 2015 May-Jul;44-46:7-13
Evaluation of ¹¹¹In-Labelled Exendin-4 Derivatives Containing Different Meprin β-Specific Cleavable Linkers.
Jodal A, Pape F, Becker-Pauly C, Maas O, Schibli R, Béhé M.
PLoS One. 2015 Apr 9;10(4):e0123443
2014
Development of high throughput screening assays and pilot screen for inhibitors of metalloproteases meprin α and β.
Madoux F, Tredup C, Spicer TP, Scampavia L, Chase PS, Hodder PS, Fields GB, Becker-Pauly C, Minond D.
Biopolymers. 2014 Sep;102(5):396-406
Microbial-induced meprin β cleavage in MUC2 mucin and a functional CFTR channel are required to release anchored small intestinal mucus.
Schütte A, Ermund A, Becker-Pauly C, Johansson ME, Rodriguez-Pineiro AM, Bäckhed F, Müller S, Lottaz D, Bond JS, Hansson GC.
Proc Natl Acad Sci U S A. 2014 Aug 26;111(34):12396-401
Mapping orphan proteases by proteomics: Meprin metalloproteases deciphered as potential therapeutic targets.
Becker-Pauly C, Broder C, Prox J, Koudelka T, Tholey A.
Proteomics Clin Appl. 2014 Jun;8(5-6):382-8
LC-MS based cleavage site profiling of the proteases ADAM10 and ADAM17 using proteome-derived peptide libraries.
Tucher J, Linke D, Koudelka T, Cassidy L, Tredup C, Wichert R, Pietrzik C, Becker-Pauly C, Tholey A.
J Proteome Res. 2014 Apr 4;13(4):2205-14
2013
Short-term TNFα shedding is independent of cytoplasmic phosphorylation or furin cleavage of ADAM17.
Schwarz J, Broder C, Helmstetter A, Schmidt S, Yan I, Müller M, Schmidt-Arras D, Becker-Pauly C, Koch-Nolte F, Mittrücker HW, Rabe B, Rose-John S, Chalaris A.
Biochim Biophys Acta. 2013 Dec;1833(12):3355-3367
Metalloproteases meprin α and meprin β are C- and N-procollagen proteinases important for collagen assembly and tensile strength.
Broder C, Arnold P, Vadon-Le Goff S, Konerding MA, Bahr K, Müller S, Overall CM, Bond JS, Koudelka T, Tholey A, Hulmes DJ, Moali C, Becker-Pauly C.
Proc Natl Acad Sci U S A. 2013 Aug 27;110(35):14219-24
TNFα cleavage beyond TACE/ADAM17: matrix metalloproteinase 13 is a potential therapeutic target in sepsis and colitis.
Becker-Pauly C, Rose-John S.
EMBO Mol Med. 2013 Jul;5(7):970-2
The metalloproteases meprin α and meprin β: unique enzymes in inflammation, neurodegeneration, cancer and fibrosis.
Broder C, Becker-Pauly C.
Biochem J. 2013 Mar 1;450(2):253-64
The substrate degradome of meprin metalloproteases reveals an unexpected proteolytic link between meprin β and ADAM10.
Jefferson T, Auf dem Keller U, Bellac C, Metz VV, Broder C, Hedrich J, Ohler A, Maier W, Magdolen V, Sterchi E, Bond JS, Jayakumar A, Traupe H, Chalaris A, Rose-John S, Pietrzik CU, Postina R, Overall CM, Becker-Pauly C.
Cell Mol Life Sci. 2013 Jan;70(2):309-33
2012
Meprins process matrix metalloproteinase-9 (MMP-9)/gelatinase B and enhance the activation kinetics by MMP-3.
Geurts N, Becker-Pauly C, Martens E, Proost P, Van den Steen PE, Stöcker W, Opdenakker G.
FEBS Lett. 2012 Dec 14;586(24):4264-9
Structural basis for the sheddase function of human meprin β metalloproteinase at the plasma membrane.
Arolas JL, Broder C, Jefferson T, Guevara T, Sterchi EE, Bode W, Stöcker W, Becker-Pauly C, Gomis-Rüth FX.
Proc Natl Acad Sci U S A. 2012 Oct 2;109(40):16131-6
Meprin α transactivates the epidermal growth factor receptor (EGFR) via ligand shedding, thereby enhancing colorectal cancer cell proliferation and migration.
Minder P, Bayha E, Becker-Pauly C, Sterchi EE.
JJ Biol Chem. 2012 Oct 12;287(42):35201-1
Sizzled is unique among secreted frizzled-related proteins for its ability to specifically inhibit bone morphogenetic protein-1 (BMP-1)/tolloid-like proteinases.
Bijakowski C, Vadon-Le Goff S, Delolme F, Bourhis JM, Lécorché P, Ruggiero F, Becker-Pauly C, Yiallouros I, Stöcker W, Dive V, Hulmes DJ, Moali C.
J Biol Chem. 2012 Sep 28;287(40):33581-93
The metalloprotease meprin β generates amino terminal-truncated amyloid β peptide species.
Bien J, Jefferson T, Causević M, Jumpertz T, Munter L, Multhaup G, Weggen S, Becker-Pauly C, Pietrzik CU.
J Biol Chem. 2012 Sep 28;287(40):33304-13
TMPRSS4 is a type II transmembrane serine protease involved in cancer and viral infections.
Ohler A, Becker-Pauly C.
Biol Chem. 2012 Sep;393(9):907-14
2011
Enhanced activity of meprin-α, a pro-migratory and pro-angiogenic protease, in colorectal cancer.
Lottaz D, Maurer CA, Noël A, Blacher S, Huguenin M, Nievergelt A, Niggli V, Kern A, Müller S, Seibold F, Friess H, Becker-Pauly C, Stöcker W, Sterchi EE.
PLoS One. 2011;6(11):e26450
Proteomic identification of protease cleavage sites characterizes prime and non-prime specificity of cysteine cathepsins B, L, and S.
Biniossek ML, Nägler DK, Becker-Pauly C, Schilling O.
J Proteome Res. 2011 Dec 2;10(12):5363-73
A role for metalloendopeptidases in the breakdown of the gut hormone, PYY 3-36.
Addison ML, Minnion JS, Shillito JC, Suzuki K, Tan TM, Field BC, Germain-Zito N, Becker-Pauly C, Ghatei MA, Bloom SR, Murphy KG.
Endocrinology. 2011 Dec;152(12):4630-40
Proteomicanalyses reveal an acidic prime side specificity for the astacin metalloprotease family reflected by physiological substrates.
Becker-Pauly C, Barré O, Schilling O, Auf dem Keller U, Ohler A, Broder C, Schütte A, Kappelhoff R, Stöcker W, Overall CM.
Mol Cell Proteomics. 2011 Sep;10(9):M111.009233
Metalloprotease meprin beta generates nontoxic N-terminal amyloid precursor protein fragments in vivo.
Jefferson T, Čaušević M, auf dem Keller U, Schilling O, Isbert S, Geyer R, Maier W, Tschickardt S, Jumpertz T, Weggen S, Bond JS, Overall CM, Pietrzik CU, Becker-Pauly C.
J Biol Chem. 2011 Aug 5;286(31):27741-50
Role of meprins to protect ileal mucosa of Crohn's disease patients from colonization by adherent-invasive E. coli.
Vazeille E, Bringer MA, Gardarin A, Chambon C, Becker-Pauly C, Pender SL, Jakob C, Müller S, Lottaz D, Darfeuille-Michaud A.
PLoS One. 2011;6(6):e21199
Morpholino knockdown of the ubiquitously expressed transmembrane serine protease TMPRSS4a in zebrafish embryos exhibits severe defects in organogenesis and cell adhesion.
Ohler A, Becker-Pauly C.
Biol Chem. 2011 Jul;392(7):653-64
2010
Processing of procollagen III by meprins: new players in extracellular matrix assembly?
Kronenberg D, Bruns BC, Moali C, Vadon-Le Goff S, Sterchi EE, Traupe H, Böhm M, Hulmes DJ, Stöcker W, Becker-Pauly C.
J Invest Dermatol. 2010 Dec;130(12):2727-35
Fetuin-A and cystatin C are endogenous inhibitors of human meprin metalloproteases.
Hedrich J, Lottaz D, Meyer K, Yiallouros I, Jahnen-Dechent W, Stöcker W, Becker-Pauly C.
Biochemistry. 2010 Oct 5;49(39):8599-607
Analyzing the protease web in skin: meprin metalloproteases are activated specifically by KLK4, 5 and 8 vice versa leading to processing of proKLK7 thereby triggering its activation.
Ohler A, Debela M, Wagner S, Magdolen V, Becker-Pauly C.
Biol Chem. 2010 Apr;391(4):455-60
Let it flow: Morpholino knockdown in zebrafish embryos reveals a pro-angiogenic effect of the metalloprotease meprin alpha2.
Schütte A, Hedrich J, Stöcker W, Becker-Pauly C.
PLoS One. 2010 Jan 21;5(1):e8835
Specific processing of tenascin-C by the metalloprotease meprinbeta neutralizes its inhibition of cell spreading.
Ambort D, Brellier F, Becker-Pauly C, Stöcker W, Andrejevic-Blant S, Chiquet M, Sterchi EE.
Matrix Biol. 2010 Jan;29(1):31-42
2009
Transglutaminase-1 and bathing suit ichthyosis: molecular analysis of gene/environment interactions.
Aufenvenne K, Oji V, Walker T, Becker-Pauly C, Hennies HC, Stöcker W, Traupe H.
J Invest Dermatol. 2009 Aug;129(8):2068-71
Becker-Pauly C, Bruns BC, Damm O, Schütte A, Hammouti K, Burmester T, Stöcker W.
J Mol Biol. 2009 Jan 9;385(1):236-48
2008
Metalloprotease meprin beta in rat kidney: glomerular localization and differential expression in glomerulonephritis.
Oneda B, Lods N, Lottaz D, Becker-Pauly C, Stöcker W, Pippin J, Huguenin M, Ambort D, Marti HP, Sterchi EE.
PLoS One. 2008 May 28;3(5):e2278
2007
Two alpha subunits and one beta subunit of meprin zinc-endopeptidases are differentially expressed in the zebrafish Danio rerio.
Schütte A, Lottaz D, Sterchi EE, Stöcker W, Becker-Pauly C.
Biol Chem. 2007 May;388(5):523-31
The alpha and beta subunits of the metalloprotease meprin are expressed in separate layers of human epidermis, revealing different functions in keratinocyte proliferation and differentiation.
Becker-Pauly C, Höwel M, Walker T, Vlad A, Aufenvenne K, Oji V, Lottaz D, Sterchi EE, Debela M, Magdolen V, Traupe H, Stöcker W.
J Invest Dermatol. 2007 May;127(5):1115-25
Identification and characterization of onchoastacin, an astacin-like metalloproteinase from the filaria Onchocerca volvulus.
Borchert N, Becker-Pauly C, Wagner A, Fischer P, Stöcker W, Brattig NW.
Microbes Infect. 2007 Apr;9(4):498-506
2006
The interaction of recombinant subdomains of the procollagen C-proteinase with procollagen I provides a quantitative explanation for functional differences between the two splice variants, mammalian tolloid and bone morphogenetic protein 1.
Hintze V, Höwel M, Wermter C, Grosse Berkhoff E, Becker-Pauly C, Beermann B, Yiallouros I, Stöcker W.
Biochemistry. 2006 May 30;45(21):6741-8
2004
Human meprin alpha and beta homo-oligomers: cleavage of basement membrane proteins and sensitivity to metalloprotease inhibitors.
Kruse MN, Becker C, Lottaz D, Köhler D, Yiallouros I, Krell HW, Sterchi EE, Stöcker W.
Biochem J. 2004 Mar 1;378(Pt 2):383-9
2003
Differences in the activation mechanism between the alpha and beta subunits of human meprin.
Becker C, Kruse MN, Slotty KA, Köhler D, Harris JR, Rösmann S, Sterchi EE, Stöcker W.
Biol Chem. 2003 May;384(5):825-31
Books
Metalloproteases Meprin α and Meprin β in Health and Disease.
Tredup C and Becker-Pauly C
Encyclopedia of Cell Biology. Editors-in-Chief: Ralph A Bradshaw and Philip D Stahl, Elsevier.
Meprin and ADAM Metalloproteases: Two sides of the same coin?
Becker-Pauly C. & Rose-John S.
Matrix Metalloproteinase Biology, First Edition. Edited by Irit Sagi & Jean Gaffney. John Wiley & Sons
Other astacin homologues
Stöcker W, Möhrlen F, Becker-Pauly C
In: Handbook of Proteolytic Enzymes, 3rd ed, Salvesen G, Rawlings ND, eds, Elsevier, 956-961
Kallikrein-Related Peptidases within the Proteolytic Web (editor Dr. Viktor Magdolen a.o. (ed.)
Beaufort N, Magdolen V., Sommerhoff C.P., Becker-Pauly C
Kallikrein-Related Peptidases: Characterization, regulation, and interactions within the protease web.
De Gruyter GmbH & Co. KG, Berlin / New York)
The Metalloproteases Meprin α and β: Pathophysiological roles in Inflammation, Cardiovascular Disease, Cancer, and Fibrosis.
Becker-Pauly, C.
(invited book chapter in: Dr. Ben Dunn (ed.) Proteinases as Drug Targets, RSC Publishing)
Insect cells for heterologous production of recombinant proteins.
Becker-Pauly, C. & Stöcker, W.
(invited book chapter in: Dr. Andreas Vilcinskas (ed.) Insect Biotechnology, Springer Publishing)