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Rothweiler, Ulli



Biophysical characterization of enzymes and kinases involved in neurodegenerative diseases 


The Dual-specificity Tyrosine phosphorylation-Regulated Kinases (DYRKs) just came recently into focus of the research. It is a family of five kinases, which are involved in proliferation and differentiation. The DYRK1A gene is located in the Down syndrome critical region and its regulative role in cellular processes related to proliferation and differentiation of neuronal progenitor cells during early development which led the focus of the research on neuronal degenerative diseases like Alzheimer’s and Down syndrome.

However, DYRK1A is overexpressed in a variety of cancer cells and suspected to be the cause for the higher cancer susceptibility of children with Down syndrome to develop acute megakaryoplastic leukemia (AMKL) or acute lymphoblastic leukemia (ALL) and DYRK1A is found at elevated concentrations in brain tumors.

A second family member DYRK1B mediates survival and differentiation and can be found in an up to 10fold elevated level in solid tumors. DYRKIB blocks the cell cycling in the G0 phase and increases the expression of antioxidant genes that decrease reactive oxygen species (ROS) levels. Both mechanism lead to an increase the cell viability of quiescent cells. Quiescent cells are a major problem in the treatment of cancer. They are relatively insensitive to most chemotherapies or radiation therapies that mainly target dividing cells and can therefor escape these kind of treatments, causing a risk that these cells reenter the cell cycle, regrow and in consequence lead to a recurrence of the tumor.

Arbeider i CRIStin

  • Tuveng, Tina Rise; Rothweiler, Ulli; Udatha, D.B.R.K. Gupta; Vaaje-Kolstad, Gustav; Smalås, Arne O.; Eijsink, Vincent. Structure and function of a CE4 deacetylase isolated from a marine environment. PLoS ONE 2017; Volum 12 (11). ISSN 1932-6203.s doi: 10.1371/journal.pone.0187544.

  • Rothweiler, Ulli; Stensen, Wenche; Brandsdal, Bjørn Olav; Isaksson, Johan; Leeson, Frederick Alan; Engh, Richard Alan; Svendsen, John Sigurd Mjøen. Probing the ATP-Binding Pocket of Protein Kinase DYRK1A with Benzothiazole Fragment Molecules. Journal of Medicinal Chemistry 2016; Volum 59 (21). ISSN 0022-2623.s 9814 - 9824.s doi: 10.1021/acs.jmedchem.6b01086.

  • Rothweiler, Ulli; Eriksson, Jonas; Stensen, Wenche; Leeson, Frederick Alan; Engh, Richard Alan; Svendsen, John Sigurd. Luciferin and derivatives as a DYRK selective scaffold for the design of protein kinase inhibitors. European Journal of Medicinal Chemistry 2015; Volum 94. ISSN 0223-5234.s 140 - 148.s doi: 10.1016/j.ejmech.2015.02.035.

  • Gani, Osman A.B.S.M.; Thakkar, Balmukund; Narayanan, Dilip; Alam, Kazi Asraful; Kyomuhendo, Peter; Rothweiler, Ulli; Tello-Franco, Veronica; Engh, Richard Alan. Assessing protein kinase target similarity: Comparing sequence, structure, and cheminformatics approaches. Biochimica et Biophysica Acta - Proteins and Proteomics 2015; Volum 1854 (10). ISSN 1570-9639.s 1605 - 1616.s doi: 10.1016/j.bbapap.2015.05.004.

  • Alexeeva, Marina; Åberg, espen; Engh, Richard Alan; Rothweiler, Ulli. The structure of a dual-specificity tyrosine phosphorylation-regulated kinase 1A-PKC412 complex reveals disulfide-bridge formation with the anomalous catalytic loop HRD(HCD) cysteine.. Acta Crystallographica Section D: Biological Crystallography 2015; Volum 71. ISSN 0907-4449.s 1207 - 1215.s doi: 10.1107/S1399004715005106.

  • Williamson, Adele Kim; Rothweiler, Ulli; Leiros, Hanna-Kirsti S.. Enzyme-adenylate structure of a bacterial ATP-dependent DNA ligase with a minimized DNA-binding surface. Acta Crystallographica Section D: Biological Crystallography 2014; Volum 70 (11). ISSN 0907-4449.s 3043 - 3056.s doi: 10.1107/S1399004714021099.

  • Åberg, espen; Lund, Bjarte Aarmo; Pflug, Alexander; Gani, Osman A.B.S.M.; Rothweiler, Ulli; Oliveira, Taiana Maia De; Engh, Richard Alan. Structural origins of AGC protein kinase inhibitor selectivities: PKA as a drug discovery tool. Biological chemistry (Print) 2012; Volum 393 (10). ISSN 1431-6730.s 1121 - 1129.s doi: 10.1515/hsz-2012-0248.

  • Rothweiler, Ulli; Åberg, espen; Johnson, Kenneth; Hansen, Tom Egil; Jørgensen, Jorunn B; Engh, Richard Alan. p38 alpha MAP Kinase Dimers with Swapped Activation Segments and a Novel Catalytic Loop Conformation. Journal of Molecular Biology 2011; Volum 411 (2). ISSN 0022-2836.s 474 - 485.s doi: 10.1016/j.jmb.2011.06.013.

  • Orth, Michael; Mayer, Bernd; Rehm, Kinga; Rothweiler, Ulli; Heidmann, Doris; Holak, Tad A; Stemmann, Olaf. Shugoshin is a Mad1/Cdc20-like interactor of Mad2. EMBO Journal 2011; Volum 30 (14). ISSN 0261-4189.s 2868 - 2880.

  • Rothweiler, Ulli; Czarna, Anna Lucja; Krajewski, Marcin; Ciombor, Jolanta; Kalinski, Cédric; Khazak, Vladimir; Ross, Günther; Skobeleva, Natalia; Weber, Lutz; Holak, Tad A. Isoquinolin-1-one Inhibitors of the MDM2–p53 Interaction. ChemMedChem 2008. ISSN 1860-7179.

  • Rothweiler, Ulli; Czarna, Anna Lucja; Weber, Lutz; Popowicz, Grzegorz; Brongel, Kinga; Kowalska, Kaja; Orth, Michael; Stemmann, Olaf; Holak, Tad A. NMR Screening for Lead Compounds Using Tryptophan-Mutated Proteins. Journal of Medicinal Chemistry 2008. ISSN 0022-2623.

  • Krajewski, Marcin; Rothweiler, Ulli; D'Silva, Loyola; Majumdar, Sudipta; Klein, Christian; Holak, Tad A. An NMR-based antagonist induced dissociation assay for targeting the ligand-protein and protein-protein interactions in competition binding experiments.. Journal of Medicinal Chemistry 2007. ISSN 0022-2623.

  • Popowicz, Grzegorz; Czarna, Anna Lucja; Rothweiler, Ulli; Szwagierczak, Aleksandra; Krajewski, Marcin; Weber, Lutz; Holak, Tad A. Molecular Basis for the Inhibition of p53 by Mdmx. Cell Cycle 2007. ISSN 1538-4101.

  • D'Silva, Loyola; Ozdowy, Przemyslaw; Krajewski, Marcin; Rothweiler, Ulli; Singh, Mahavir; Holak, Tad A. Monitoring the Effects of Antagonists on Protein−Protein Interactions with NMR Spectroscopy. Journal of the American Chemical Society 2005. ISSN 0002-7863.

  • Krajewski, Marcin; Ozdowy, Przemyslaw; D'Silva, Loyola; Rothweiler, Ulli; Holak, Tad A. NMR indicates that the small molecule RITA does not block p53-MDM2 binding in vitro. Nature Medicine 2005. ISSN 1078-8956.

  • Pierechod, Marcin Miroslaw; Rothweiler, Ulli; de Oliveira, Taianá Maia. The structure of Salinibacter ruber Single‐Strand Binding protein reveals a novel, octameric architecture of bacterial SSB proteins. Norwegian Biochemical Society contact meeting 2016-01-21 - 2016-01-23 2016.

  • Alam, Kazi Asraful; Rothweiler, Ulli; Engh, Richard Alan. Static and dynamic interactions between the glycine-rich loop of protein kinases and ATP site inhibitors. Norwegian Biochemical Society contact meeting 2016-01-21 - 2016-01-24 2016.

  • Berg, Tor Olav; Halsør, Marie-Josée Haglund; Gurung, Man Kumari; Altermark, Bjørn; Leiros, Ingar; Rothweiler, Ulli; Helland, Ronny; Smalås, Arne O.; Ræder, Inger Lin Uttakleiv. From marine rest raw materials to sialic acids: Using enzymes for biomass conversion. Frontiers in Sialic Acid Research 2016-04-23 - 2016-04-25 2016.

  • Rothweiler, Ulli. DYRK1A-PKC412 complex - disulfide-bridge formation with an anomalous catalytic loop HRD(HCD) cysteine. Contact Meeting 2016 2016-01-21 - 2016-01-24 2016.

  • Alexeeva, Marina; Åberg, espen; Engh, Richard Alan; Rothweiler, Ulli. The structure of a dual-specificity tyrosine phosphorylation-regulated kinase 1A-PKC412 complex reveals disulfide-bridge formation with the anomalous catalytic loop HRD(HCD) cysteine.. Contact Meeting 2016 2016-01-21 - 2016-01-24 2016.

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