Geiss‐Friedlander, Ruth

[["dc.bibliographiccitation.firstpage","E1437"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences"],["dc.bibliographiccitation.lastpage","E1445"],["dc.bibliographiccitation.volume","115"],["dc.contributor.author","Ross, Breyan"],["dc.contributor.author","Krapp, Stephan"],["dc.contributor.author","Augustin, Martin"],["dc.contributor.author","Kierfersauer, Reiner"],["dc.contributor.author","Arciniega, Marcelino"],["dc.contributor.author","Geiss-Friedlander, Ruth"],["dc.contributor.author","Huber, Robert"],["dc.date.accessioned","2020-12-10T18:12:48Z"],["dc.date.available","2020-12-10T18:12:48Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1073/pnas.1717565115"],["dc.identifier.eissn","1091-6490"],["dc.identifier.issn","0027-8424"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/74504"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Structures and mechanism of dipeptidyl peptidases 8 and 9, important players in cellular homeostasis and cancer"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","44320"],["dc.bibliographiccitation.issue","53"],["dc.bibliographiccitation.journal","Journal of Biological Chemistry"],["dc.bibliographiccitation.lastpage","44329"],["dc.bibliographiccitation.volume","287"],["dc.contributor.author","Pilla, Esther"],["dc.contributor.author","Moeller, Ulrike"],["dc.contributor.author","Sauer, Guido"],["dc.contributor.author","Mattiroli, Francesca"],["dc.contributor.author","Melchior, Frauke"],["dc.contributor.author","Geiss-Friedlander, Ruth"],["dc.date.accessioned","2018-11-07T09:02:09Z"],["dc.date.available","2018-11-07T09:02:09Z"],["dc.date.issued","2012"],["dc.description.abstract","Sumoylation affects many cellular processes by regulating the interactions of modified targets with downstream effectors. Here we identified the cytosolic dipeptidyl peptidase 9 (DPP9) as a SUMO1 interacting protein. Surprisingly, DPP9 binds to SUMO1 independent of the well known SUMO interacting motif, but instead interacts with a loop involving Glu(67) of SUMO1. Intriguingly, DPP9 selectively associates with SUMO1 and not SUMO2, due to a more positive charge in the SUMO1-loop. We mapped the SUMO-binding site of DPP9 to an extended arm structure, predicted to directly flank the substrate entry site. Importantly, whereas mutants in the SUMO1-binding arm are less active compared with wild-type DPP9, SUMO1 stimulates DPP9 activity. Consistent with this, silencing of SUMO1 leads to a reduced cytosolic prolyl-peptidase activity. Taken together, these results suggest that SUMO1, or more likely, a sumoylated protein, acts as an allosteric regulator of DPP9."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft [2234/1-1]; European Union NoE Rubicon"],["dc.identifier.doi","10.1074/jbc.M112.397224"],["dc.identifier.isi","000312938600029"],["dc.identifier.pmid","23152501"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/24610"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Biochemistry Molecular Biology Inc"],["dc.relation.issn","0021-9258"],["dc.title","A Novel SUMO1-specific Interacting Motif in Dipeptidyl Peptidase 9 (DPP9) That Is Important for Enzymatic Regulation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3737"],["dc.bibliographiccitation.issue","19"],["dc.bibliographiccitation.journal","FEBS Journal"],["dc.bibliographiccitation.lastpage","3757"],["dc.bibliographiccitation.volume","282"],["dc.contributor.author","Zhang, Hui"],["dc.contributor.author","Maqsudi, Sadiqa"],["dc.contributor.author","Rainczuk, Adam"],["dc.contributor.author","Duffield, Nadine"],["dc.contributor.author","Lawrence, Josie"],["dc.contributor.author","Keane, Fiona M."],["dc.contributor.author","Justa-Schuch, Daniela"],["dc.contributor.author","Geiss-Friedlander, Ruth"],["dc.contributor.author","Gorrell, Mark D."],["dc.contributor.author","Stephens, Andrew N."],["dc.date.accessioned","2018-11-07T09:50:57Z"],["dc.date.available","2018-11-07T09:50:57Z"],["dc.date.issued","2015"],["dc.description.abstract","Dipeptidyl peptidase 9 (DPP9) is a member of the S9B/DPPIV (DPP4) serine protease family, which cleaves N-terminal dipeptides at an Xaa-Pro consensus motif. Cytoplasmic DPP9 has roles in epidermal growth factor signalling and in antigen processing, whilst the role of the recently discovered nuclear form of DPP9 is unknown. Mice lacking DPP9 proteolytic activity die as neonates. We applied a modified 2D differential in-gel electrophoresis approach to identify novel DPP9 substrates, using mouse embryonic fibroblasts lacking endogenous DPP9 activity. A total of 111 potential new DPP9 substrates were identified, with nine proteins/peptides confirmed as DPP9 substrates by MALDI-TOF or immunoblotting. Moreover, we also identified the dipeptide Val-Ala as a consensus site for DPP9 cleavage that was not recognized by DPP8, suggesting different in vivo roles for these closely related enzymes. The relative kinetics for the cleavage of these nine candidate substrates by DPP9, DPP8 and DPP4 were determined. This is the first identification of DPP9 substrates from cells lacking endogenous DPP9 activity. These data greatly expand the potential roles of DPP9 and suggest different in vivo roles for DPP9 and DPP8."],["dc.identifier.doi","10.1111/febs.13371"],["dc.identifier.isi","000362365200006"],["dc.identifier.pmid","26175140"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/35814"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","1742-4658"],["dc.relation.issn","1742-464X"],["dc.title","Identification of novel dipeptidyl peptidase 9 substrates by two-dimensional differential in-gel electrophoresis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["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","947"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Nature Reviews Molecular Cell Biology"],["dc.bibliographiccitation.lastpage","956"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Geiss-Friedlander, Ruth"],["dc.contributor.author","Melchior, Frauke"],["dc.date.accessioned","2018-11-07T10:49:57Z"],["dc.date.available","2018-11-07T10:49:57Z"],["dc.date.issued","2007"],["dc.description.abstract","A decade has passed since SUMO (small ubiquitin-related modifier) was discovered to be a reversible post-translational protein modifier. During this time many enzymes that participate in regulated SUMO-conjugation and -deconjugation pathways have been identified and characterized. In parallel, the search for SUMO substrates has produced a long list of targets, which appear to be involved in most cellular functions. Sumoylation is a highly dynamic process and its outcomes are extremely diverse, ranging from changes in localization to altered activity and, in some cases, stability of the modified protein. At first glance, these effects have nothing in common; however, it seems that they all result from changes in the molecular interactions of the sumoylated proteins."],["dc.identifier.doi","10.1038/nrm2293"],["dc.identifier.isi","000251173600008"],["dc.identifier.pmid","18000527"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/48546"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","1471-0072"],["dc.title","Concepts in sumoylation: a decade on"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","e228"],["dc.bibliographiccitation.issue","a2"],["dc.bibliographiccitation.journal","Acta Crystallographica Section A Foundations and Advances"],["dc.bibliographiccitation.lastpage","e228"],["dc.bibliographiccitation.volume","74"],["dc.contributor.author","Ross, Breyan"],["dc.contributor.author","Krapp, Stephan"],["dc.contributor.author","Geiss-Friedlander, Ruth"],["dc.contributor.author","Huber, Robert"],["dc.date.accessioned","2020-12-10T18:26:04Z"],["dc.date.available","2020-12-10T18:26:04Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1107/S2053273318091738"],["dc.identifier.issn","2053-2733"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/75936"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","DPP8 and DPP9 structure, mechanism and interaction with SUMO1"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","27211"],["dc.bibliographiccitation.issue","40"],["dc.bibliographiccitation.journal","Journal of Biological Chemistry"],["dc.bibliographiccitation.lastpage","27219"],["dc.bibliographiccitation.volume","284"],["dc.contributor.author","Geiss-Friedlander, Ruth"],["dc.contributor.author","Parmentier, Nicolas"],["dc.contributor.author","Moeller, Ulrike"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","van den Eynde, Benoit J."],["dc.contributor.author","Melchior, Frauke"],["dc.date.accessioned","2018-11-07T11:23:15Z"],["dc.date.available","2018-11-07T11:23:15Z"],["dc.date.issued","2009"],["dc.description.abstract","Protein degradation is an essential process that continuously takes place in all living cells. Regulated degradation of most cellular proteins is initiated by proteasomes, which produce peptides of varying length. These peptides are rapidly cleaved to single amino acids by cytoplasmic peptidases. Proline-containing peptides pose a specific problem due to structural constrains imposed by the pyrrolidine ring that prevents most peptidases from cleavage. Here we show that DPP9, a poorly characterized cytoplasmic prolyl-peptidase, is rate-limiting for destruction of proline-containing substrates both in cell extracts and in intact cells. We identified the first natural substrate for DPP9, the RU1(34-42) antigenic peptide (VPYGSFKHV). RU1(34-42) is degraded in vitro by DPP9, and down-regulation of DPP9 in intact cells results in increased presentation of this antigen. Together our findings demonstrate an important role for DPP9 in peptide turnover and antigen presentation."],["dc.identifier.doi","10.1074/jbc.M109.041871"],["dc.identifier.isi","000270232300021"],["dc.identifier.pmid","19667070"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6080"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/56161"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Biochemistry Molecular Biology Inc"],["dc.relation.issn","0021-9258"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","The Cytoplasmic Peptidase DPP9 Is Rate-limiting for Degradation of Proline-containing Peptides"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","EMBO reports"],["dc.contributor.author","Bolgi, Oguz"],["dc.contributor.author","Silva‐Garcia, Maria"],["dc.contributor.author","Ross, Breyan"],["dc.contributor.author","Pilla, Esther"],["dc.contributor.author","Kari, Vijayalakshmi"],["dc.contributor.author","Killisch, Markus"],["dc.contributor.author","Spitzner, Melanie"],["dc.contributor.author","Stark, Nadine"],["dc.contributor.author","Lenz, Christof"],["dc.contributor.author","Weiss, Konstantin"],["dc.contributor.author","Geiss‐Friedlander, Ruth"],["dc.date.accessioned","2022-09-01T09:51:03Z"],["dc.date.available","2022-09-01T09:51:03Z"],["dc.date.issued","2022"],["dc.identifier.doi","10.15252/embr.202154136"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/113867"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-597"],["dc.relation.eissn","1469-3178"],["dc.relation.issn","1469-221X"],["dc.title","Dipeptidyl peptidase 9 triggers\n BRCA2\n degradation and promotes\n DNA\n damage repair"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","695"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Acta Neuropathologica"],["dc.bibliographiccitation.lastpage","713"],["dc.bibliographiccitation.volume","129"],["dc.contributor.author","Kunadt, Marcel"],["dc.contributor.author","Eckermann, Katrin"],["dc.contributor.author","Stuendl, Anne"],["dc.contributor.author","Gong, Jing"],["dc.contributor.author","Russo, Belisa"],["dc.contributor.author","Strauss, Katrin"],["dc.contributor.author","Rai, Surya"],["dc.contributor.author","Kügler, Sebastian"],["dc.contributor.author","Falomir Lockhart, Lisandro"],["dc.contributor.author","Schwalbe, Martin"],["dc.contributor.author","Krumova, Petranka"],["dc.contributor.author","Oliveira, Luis M. A."],["dc.contributor.author","Bähr, Mathias"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Levin, Johannes"],["dc.contributor.author","Giese, Armin"],["dc.contributor.author","Kruse, Niels"],["dc.contributor.author","Mollenhauer, Brit"],["dc.contributor.author","Geiss‐Friedlander, Ruth"],["dc.contributor.author","Ludolph, Albert C."],["dc.contributor.author","Freischmidt, Axel"],["dc.contributor.author","Feiler, Marisa S."],["dc.contributor.author","Danzer, Karin M."],["dc.contributor.author","Zweckstetter, Markus"],["dc.contributor.author","Jovin, Thomas M."],["dc.contributor.author","Simons, Mikael"],["dc.contributor.author","Weishaupt, Jochen H."],["dc.contributor.author","Schneider, Anja"],["dc.date.accessioned","2017-09-07T11:44:25Z"],["dc.date.available","2017-09-07T11:44:25Z"],["dc.date.issued","2015"],["dc.description.abstract","Extracellular alpha-Synuclein has been implicated in interneuronal propagation of disease pathology in Parkinson's Disease. How alpha-Synuclein is released into the extracellular space is still unclear. Here, we show that alpha-Synuclein is present in extracellular vesicles in the central nervous system. We find that sorting of alpha-Synuclein in extracellular vesicles is regulated by sumoylation and that sumoylation acts as a sorting factor for targeting of both, cytosolic and transmembrane proteins, to extracellular vesicles. We provide evidence that the SUMO-dependent sorting utilizes the endosomal sorting complex required for transport (ESCRT) by interaction with phosphoinositols. Ubiquitination of cargo proteins is so far the only known determinant for ESCRT-dependent sorting into the extracellular vesicle pathway. Our study reveals a function of SUMO protein modification as a Ubiquitin-independent ESCRT sorting signal, regulating the extracellular vesicle release of alpha-Synuclein. We deciphered in detail the molecular mechanism which directs alpha-Synuclein into extracellular vesicles which is of highest relevance for the understanding of Parkinson's disease pathogenesis and progression at the molecular level. We furthermore propose that sumo-dependent sorting constitutes a mechanism with more general implications for cell biology."],["dc.identifier.doi","10.1007/s00401-015-1408-1"],["dc.identifier.gro","3141916"],["dc.identifier.isi","000352716500007"],["dc.identifier.pmid","25778619"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11731"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/2500"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.eissn","1432-0533"],["dc.relation.issn","0001-6322"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Extracellular vesicle sorting of alpha-Synuclein is regulated by sumoylation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2519"],["dc.bibliographiccitation.issue","23"],["dc.bibliographiccitation.journal","EMBO Journal"],["dc.bibliographiccitation.lastpage","2535"],["dc.bibliographiccitation.volume","35"],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Chakrabarti, Rituparna"],["dc.contributor.author","Al‐Moyed, Hanan"],["dc.contributor.author","Müller, Alexandra"],["dc.contributor.author","Hoch, Gerhard"],["dc.contributor.author","Pangrsic, Tina"],["dc.contributor.author","Yamanbaeva, Gulnara"],["dc.contributor.author","Lenz, Christof"],["dc.contributor.author","Pan, Kuan‐Ting"],["dc.contributor.author","Auge, Elisabeth"],["dc.contributor.author","Geiss‐Friedlander, Ruth"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Brose, Nils"],["dc.contributor.author","Wichmann, Carolin"],["dc.contributor.author","Reisinger, Ellen"],["dc.date.accessioned","2017-09-07T11:52:19Z"],["dc.date.available","2017-09-07T11:52:19Z"],["dc.date.issued","2016"],["dc.identifier.doi","10.15252/embj.201694564"],["dc.identifier.gro","3144895"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/2570"],["dc.language.iso","en"],["dc.notes.intern","Crossref Import"],["dc.notes.status","final"],["dc.relation.issn","0261-4189"],["dc.title","Hair cell synaptic dysfunction, auditory fatigue and thermal sensitivity in otoferlin Ile515Thr mutants"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]