Gehring
Fakultäten » Medizinische Fakultät » Biochemisches Institut » Prof. Dr. Heinz Gehring » Gehring
Completed research project
| Title / Titel | The cellular role of the Ewing sarcoma (EWS) proto-oncoprotein and its arginine methylation | ||||
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| Abstract (PDF, 14 KB) | |||||
| Summary / Zusammenfassung | The research interest during the last years focused on structural and functional relationships of the multi-domain and multi-motif Ewing sarcoma (EWS) proto-oncoprotein. The multi-domain and multi-motif EWS protein belongs to a large family of RNA-binding proteins and has been found mainly in the nucleus. Recently, we have shown that EWS protein is not only localized in the nucleus and cytosol, but also on cell surfaces. The EWS protein was found to be extensively asymmetrically dimethylated on arginine residues. Our goal was to unravel the cellular role of these numerous post-translational modifications of EWS protein which will have important implications on various processes from gene expression and cell signalling to protein transport and thus on cell homeostasis. By applying MS-based methods we tried to identify the phosphorylation sites, as well as cellular interaction partners of EWS protein derivatives, unmodified and modified (methylated and/or phosphorylated) and truncated to various degrees. Interaction in the cell have been confirmed by fluorescence imaging technics. Knowing the interaction partners will indicate in what physiological processes EWS protein is participating and what role its post-translational modifications are playing, in particular on the cell surface. Weitere Informationen |
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| Publications / Publikationen | Belyanskaya L.L., Gehrig P.M., Gehring H. (2001) Exposure on cell surface and extensive arginine methylation of ewing sarcoma (EWS) protein. J. Biol. Chem. 276: 18681-18687.Belyanskaya L.L., Delattre O., Gehring H. (2003) Expression and subcellular localization of Ewing sarcoma (EWS) protein is affected by the methylation process. Exp Cell Res. 288: 374-381. Pahlich S., Bschir K., Chiavi C., Belyanskaya L. and Gehring H. (2005) Different methylation characteristics of protein arginine methyltransferase 1 and 3 toward the Ewing sarcoma protein and a peptide. Proteins-Structure Function and Bioinformatics 61: 164-175. Zakaryan R.P. and Gehring H. ( 2006) Identification and Characterization of the Nuclear Localization/Retention Signal in the EWS Proto-oncoprotein. J. Mol. Biol. 363: 27-38.Pahlich S., Zakaryan R.P. and Gehring H. (2006) Protein arginine methylation: Cellular functions and methods of analysis, Biochimica et Biophysica Acta 1764, 1890-1903.Pahlich S., Zakaryan R.P. and Gehring H. (2008) Identification of Proteins Interacting with Protein Arginine Methyltransferase 8: The Ewing Sarcoma (EWS) Protein Binds Independent of its Methylation State. Proteins-Structure Function and Bioinformatics. 72(4), 1125-1137Leemann-Zakaryan R.P., Pahlich S., Sedda M.S., Quero L., Grossenbacher D. and Gehring H. (2009) Dynamic Subcellular Localization of the Ewing Sarcoma Proto- Oncoprotein and Its Association with and Stabilization of Microtubules. J. Mol. Biol. 386, 1-13.Pahlich S., Quero L., Roschitzki B. Leemann-Zakaryan R.P. and Gehring H. (2009) Analysis of Ewing Sarcoma (EWS)-Binding Proteins: Interaction with hnRNP M, U, and RNA-Helicases p68/72 within Protein-RNA Complexes. Journal of Proteome Research 8, 4455–4465.Leemann-Zakaryan R. P., Pahlich S., Grossenbacher D., and Gehring H. (2011) Tyrosine Phosphorylation in the C-Terminal Nuclear Localization and Retention Signal (C-NLS) of the EWS Protein. Sarcoma, Volume 2011, Article ID 218483, 6 pages doi:10.1155/2011/218483Weitere Informationen |
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| Keywords / Suchbegriffe | arginine methylation, GST pull-down, mass spectrometry, post-translational modification, co-localization, membrane-associated proteins, RNA-binding protein, NLS, TET family | ||||
| Project leadership and contacts / Projektleitung und Kontakte |
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| Funding source(s) / Unterstützt durch |
SNF (Personen- und Projektförderung), Foundation, No project-specific funding Olga Mayenfisch Stiftung, Hartmann Müller Stiftung für medizinische Forschung, Julius Müller Stiftung zur Unterstützung der Krebsforschung |
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| In collaboration with / In Zusammenarbeit mit |
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| Duration of Project / Projektdauer | Feb 2003 to May 2011 |