Kilisch, Markus

[["dc.bibliographiccitation.firstpage","eaaz1436"],["dc.bibliographiccitation.issue","647"],["dc.bibliographiccitation.journal","Science Signaling"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Menzel, Julia"],["dc.contributor.author","Kownatzki-Danger, Daniel"],["dc.contributor.author","Tokar, Sergiy"],["dc.contributor.author","Ballone, Alice"],["dc.contributor.author","Unthan-Fechner, Kirsten"],["dc.contributor.author","Kilisch, Markus"],["dc.contributor.author","Lenz, Christof"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Mori, Mattia"],["dc.contributor.author","Ottmann, Christian"],["dc.contributor.author","Shattock, Michael J."],["dc.contributor.author","Lehnart, Stephan E."],["dc.contributor.author","Schwappach, Blanche"],["dc.date.accessioned","2021-04-14T08:32:51Z"],["dc.date.available","2021-04-14T08:32:51Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1126/scisignal.aaz1436"],["dc.identifier.pmid","32873725"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/84038"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/68"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/368"],["dc.identifier.url","https://sfb1190.med.uni-goettingen.de/production/literature/publications/126"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | A07: Rolle der TRC40-Maschinerie im Proteostase-Netzwerk von Kardiomyozyten"],["dc.relation","SFB 1190: Transportmaschinen und Kontaktstellen zellulärer Kompartimente"],["dc.relation.eissn","1937-9145"],["dc.relation.issn","1945-0877"],["dc.relation.workinggroup","RG Lehnart"],["dc.relation.workinggroup","RG Schwappach (Membrane Protein Biogenesis)"],["dc.relation.workinggroup","RG Lenz"],["dc.relation.workinggroup","RG Urlaub (Bioanalytische Massenspektrometrie)"],["dc.title","14-3-3 binding creates a memory of kinase action by stabilizing the modified state of phospholamban"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e16370"],["dc.bibliographiccitation.journal","eLife"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Justa-Schuch, Daniela"],["dc.contributor.author","Silva-Garcia, Maria"],["dc.contributor.author","Pilla, Esther"],["dc.contributor.author","Engelke, Michael"],["dc.contributor.author","Kilisch, Markus"],["dc.contributor.author","Lenz, Christof"],["dc.contributor.author","Möller, Ulrike"],["dc.contributor.author","Nakamura, Fumihiko"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Geiss-Friedlander, Ruth"],["dc.date.accessioned","2021-06-01T10:48:59Z"],["dc.date.available","2021-06-01T10:48:59Z"],["dc.date.issued","2016"],["dc.description.abstract","The aminopeptidase DPP9 removes dipeptides from N-termini of substrates having a proline or alanine in second position. Although linked to several pathways including cell survival and metabolism, the molecular mechanisms underlying these outcomes are poorly understood. We identified a novel interaction of DPP9 with Filamin A, which recruits DPP9 to Syk, a central kinase in B-cell signalling. Syk signalling can be terminated by degradation, requiring the ubiquitin E3 ligase Cbl. We show that DPP9 cleaves Syk to produce a neo N-terminus with serine in position 1. Pulse-chases combined with mutagenesis studies reveal that Ser1 strongly influences Syk stability. Furthermore, DPP9 silencing reduces Cbl interaction with Syk, suggesting that DPP9 processing is a prerequisite for Syk ubiquitination. Consistently, DPP9 inhibition stabilizes Syk, thereby modulating Syk signalling. Taken together, we demonstrate DPP9 as a negative regulator of Syk and conclude that DPP9 is a novel integral aminopeptidase of the N-end rule pathway."],["dc.description.abstract","Proteins are made up of building blocks called amino acids bonded together to form chain-like molecules. Around twenty different amino acids are used to make proteins, and enzymes called proteases can recognize specific pairs of amino acids in proteins and cut the bonds between them. Dipeptidylpeptidase 9 (or DPP9 for short) is a protease that removes two amino acids from the end of a protein, just as long the second amino acid is one of two specific kinds (namely, an alanine or a proline). The DPP9 protease influences a range of processes in the cell including cell death, signaling and survival. Indeed, mice born with an inactive version of DPP9 die shortly after birth, but it is not known why this happens. Justa-Schuch et al. investigated how the protease DPP9 controls processes inside cells and found an unexpected connection between DPP9 and another protein called Syk. The Syk protein is found in immune cells called B cells, and becomes highly activated whenever these cells are stimulated. Once activated Syk changes the activity of many proteins, affecting which genes are switched on and how the B cell moves and divides. By using DPP9 as a kind of bait, Justa-Schuch et al. found human proteins that bind to the protease. This search identified a protein called Filamin A that interacted with DPP9, placing DPP9 close to Syk, which also binds to Filamin A. Further experiments showed that when DPP9 was located close to Syk, it cut the end of Syk. This cut left the Syk protein with a different amino acid exposed at its end, which in turn made it susceptible to being broken down inside the cell. Justa-Schuch et al. went on to show that DPP9 preferentially cleaved the active form of Syk. Since cleaved Syk was subsequently broken down, DPP9 acts as a shut-off mechanism for Syk after the B cell has been stimulated. The findings show that DPP9 can influence how much and how long the B cell responds to stimulation. Inhibitors of DPP9 may therefore be useful for stabilizing Syk, which is known to stop specific tumors from growing. Future work will investigate the mechanisms that control how Filamin A, DPP9 and Syk interact."],["dc.identifier.doi","10.7554/eLife.16370"],["dc.identifier.isi","000385399800001"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13846"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/86123"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elife Sciences Publications Ltd"],["dc.relation.eissn","2050-084X"],["dc.relation.issn","2050-084X"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","DPP9 is a novel component of the N-end rule pathway targeting the tyrosine kinase Syk"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","32787"],["dc.bibliographiccitation.issue","45"],["dc.bibliographiccitation.journal","Journal of Biological Chemistry"],["dc.bibliographiccitation.lastpage","32796"],["dc.bibliographiccitation.volume","288"],["dc.contributor.author","Pilla, Esther"],["dc.contributor.author","Kilisch, Markus"],["dc.contributor.author","Lenz, Christof"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Geiss-Friedlander, Ruth"],["dc.date.accessioned","2018-11-07T09:17:38Z"],["dc.date.available","2018-11-07T09:17:38Z"],["dc.date.issued","2013"],["dc.description.abstract","Background: SUMO1 binds to an arm motif in the prolyl-peptidase DPP9, leading to allosteric activation of the peptidase. Results: A SUMO1 peptide covering the DPP9 interaction surface inhibits DPP9 activity. Inhibition is dependent on residues in the DPP9 arm motif. Conclusion: The SUMO1 peptide and its variants are allosteric DPP9 inhibitors. Significance: This work highlights the potential use of peptides mimicking interaction surfaces for modulating enzyme activity. The intracellular peptidases dipeptidyl peptidase (DPP) 8 and DPP9 are involved in multiple cellular pathways including antigen maturation, cellular homeostasis, energy metabolism, and cell viability. Previously we showed that the small ubiquitin-like protein modifier SUMO1 interacts with an armlike structure in DPP9, leading to allosteric activation of the peptidase. Here we demonstrate that the E67-interacting loop (EIL) peptide, which corresponds to the interaction surface of SUMO1 with DPP9, acts as a noncompetitive inhibitor of DPP9. Moreover, by analyzing the sensitivity of DPP9 arm mutants to the EIL peptide, we mapped specific residues in the arm that are important for inhibition by the EIL, suggesting that the peptide acts as an allosteric inhibitor of DPP9. By modifying the EIL peptide, we constructed peptide variants with more than a 1,000-fold selectivity toward DPP8 (147 nm) and DPP9 (170 nm) over DPPIV (200 m). Furthermore, application of these peptides to cells leads to a clear inhibition of cellular prolyl peptidase activity. Importantly, in line with previous publications, inhibition of DPP9 with these novel allosteric peptide inhibitors leads to an increase in EGF-mediated phosphorylation of Akt. This work highlights the potential use of peptides that mimic interaction surfaces for modulating enzyme activity."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft [2234/1-1, 1086/2]"],["dc.identifier.doi","10.1074/jbc.M113.489179"],["dc.identifier.isi","000328681700062"],["dc.identifier.pmid","24072711"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/28214"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Biochemistry Molecular Biology Inc"],["dc.relation.issn","1083-351X"],["dc.relation.issn","0021-9258"],["dc.title","The SUMO1-E67 Interacting Loop Peptide Is an Allosteric Inhibitor of the Dipeptidyl Peptidases 8 and 9"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]