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Dynamic subcellular localization of the EWS proto-oncoprotein and its association with and stabilization of microtubules


Leemann-Zakaryan, R P; Pahlich, S; Sedda, M; Quero, L; Grossenbacher, D; Gehring, H (2009). Dynamic subcellular localization of the EWS proto-oncoprotein and its association with and stabilization of microtubules. Journal of Molecular Biology, 386(1):1-13.

Abstract

Ewing sarcoma (EWS) protein is a member of a large family of RNA-binding proteins. Chimeric EWS oncoproteins generated by chromosomal translocations between the EWS protein and several transcription factors cause various malignant tumors. Due to its multifunctional properties the EWS protein is involved in processes such as meiotic DNA pairing/recombination, cellular senescence, gene expression, RNA processing and transport, as well as cell signaling. The EWS protein is predominantly located in the nucleus. It was found in cytoplasm and associated with the cell membrane. In this study the analysis of the localization of endogenous and fluorescently labeled recombinant EWS protein in different phases of cell cycle in different cell lines revealed a very dynamic subcellular distribution of the EWS protein. In Cos7 and Hela cells an association of the EWS protein with the centrosomal compartments was shown. Furthermore, in HEK 293 (T) cells an interaction of the overexpessed recombinant EWS-YFP fusion protein with microtubules was demonstrated leading to their stabilization and cell cycle arrest. As an outlook, the present findings provide an important insight into temporally and spatially regulated functions of the EWS protein and, particularly, into its role in the regulation of the cell cycle and possibly cell differentiation.

Abstract

Ewing sarcoma (EWS) protein is a member of a large family of RNA-binding proteins. Chimeric EWS oncoproteins generated by chromosomal translocations between the EWS protein and several transcription factors cause various malignant tumors. Due to its multifunctional properties the EWS protein is involved in processes such as meiotic DNA pairing/recombination, cellular senescence, gene expression, RNA processing and transport, as well as cell signaling. The EWS protein is predominantly located in the nucleus. It was found in cytoplasm and associated with the cell membrane. In this study the analysis of the localization of endogenous and fluorescently labeled recombinant EWS protein in different phases of cell cycle in different cell lines revealed a very dynamic subcellular distribution of the EWS protein. In Cos7 and Hela cells an association of the EWS protein with the centrosomal compartments was shown. Furthermore, in HEK 293 (T) cells an interaction of the overexpessed recombinant EWS-YFP fusion protein with microtubules was demonstrated leading to their stabilization and cell cycle arrest. As an outlook, the present findings provide an important insight into temporally and spatially regulated functions of the EWS protein and, particularly, into its role in the regulation of the cell cycle and possibly cell differentiation.

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11 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Department of Biochemistry
07 Faculty of Science > Department of Biochemistry
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Date:12 February 2009
Deposited On:08 Jan 2009 09:31
Last Modified:05 Apr 2016 12:48
Publisher:Elsevier
ISSN:0022-2836
Publisher DOI:https://doi.org/10.1016/j.jmb.2008.12.039

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