We have contributed to the elucidation of the function of LCK kinase interaction with T-lymphocyte co-receptors. While the interaction of LCK with CD8 is of little significance, the interaction of LCK with CD4 contributes substantially to the function of helper T-lymphocytes.
Using animal models, we have resolved the long-standing question of the biological function of the interaction of LCK kinase with CD8 and CD4 T-lymphocyte co-receptors. While the interaction of LCK with CD8 is of little importance in T-lymphocyte activation, the interaction of LCK with CD4 is essential for the development and function of helper T-lymphocytes.
Publication | Horkova V, Drobek A, Paprckova D, Niederlova V, Prasai A, Uleri V, Glatzova D, Kraller M, Cesnekova M, Janusova S, Salyova E, Tsyklauri O, Kadlecek TA, Krizova K, Platzer R, Schober K, Busch DH, Weiss A, Huppa JB, Stepanek O: Unique roles of co-receptor-bound LCK in helper and cytotoxic T cells. Nat Immunol 2023 24(1): 174-185. [pubmed] [doi] |
Contact | Ondřej Štěpánek, (+420) 296 442 155, ondrej.stepanek@img.cas.cz |
Cooperating subjects | Institute for Hygiene and Applied Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria Division of Rheumatology, Rosalind Russell and Ephraim P. Engleman Arthritis Research Center, Department of Medicine, University of California, San Francisco, CA, USA Institute for Medical Microbiology, Immunology, and Hygiene, Technical University of Munich, Munich, Germany Mikrobiologisches Institut—Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Erlangen, Germany |
SnRNAs are essential components of the complex that catalyses pre-mRNA splicing. In this study, we have described a novel structure of snRNAs and revealed the function of the Gemin3 protein that modifies these snRNAs into a functional form.
RNA splicing is a key step in the flow of genetic information from DNA to proteins. RNA splicing is catalyzed by a large complex called the spliceosome, which consists of ~200 pieces. The key components of the spliceosome are small non-coding RNAs (snRNAs). We described that newly formed snRNAs adopt a shape that blocks their incorporation into the spliceosome. We proposed structural adaptations that generate functional snRNAs and identified the enzyme that catalyses these structural changes.
Publication | Pánek J, Roithová A, Radivojević N, Sýkora M, Prusty AB, Huston N, Wan H, Pyle AM, Fischer U, Staněk D: The SMN complex drives structural changes in human snRNAs to enable snRNP assembly. Nat Commun 2023 14(1): 6580. [pubmed] [doi] |
Contact | David Staněk, (+420) 296 443 118, david.stanek@img.cas.cz |
Cooperating subjects | Institute of Microbiology of the Czech Academy of Sciences, Prague, Czech Republic Würzburg University, Würzburg, Germany Yale University, CT, USA |
Telomeres are essential for maintaining the integrity of chromosomes. In this study, we describe a novel way in which the activity of the PPM1D enzyme helps to protect telomeres in human cells.
Ends of chromosomes are protected by telomeres, and their damage leads to genomic instability, ageing and cancer development. The sheletrin complex prevents telomere shortening and fusion. In this work, we describe a novel molecular mechanism contributing to the binding of TRF2 and TIN2, two subunits of the shelterin complex. This function is regulated by the activity of ATR and PPM1D enzymes both during telomere damage and cell division. These data will be the subject of our further research.
Publication | Storchova R, Palek M, Palkova N, Veverka P, Brom T, Hofr C, Macurek L: Phosphorylation of TRF2 promotes its interaction with TIN2 and regulates DNA damage response at telomeres. Nucleic Acids Res 2023 51(3):1154-1172 [pubmed] [doi] |
Contact | Libor Macůrek, (+420) 296 443 210, libor.macurek@img.cas.cz |
Cooperating subject | Masaryk University, Brno, Czech Republic |