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Tyrosine Phosphorylation in the C-Terminal Nuclear Localization and Retention Signal (C-NLS) of the EWS Protein

Ewing sarcoma (EWS) proto-oncoprotein, an RNA-binding protein, is involved in DNA recombination and repair, gene expression, RNA processing and transport, as well as cell signalling. Chimeric EWS oncoproteins generated by chromosomal translocations between EWSR1 and the genes of transcription factor...

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Autores principales: Leemann-Zakaryan, Ruzanna P., Pahlich, Steffen, Grossenbacher, Doris, Gehring, Heinz
Formato: Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3103976/
https://www.ncbi.nlm.nih.gov/pubmed/21647358
http://dx.doi.org/10.1155/2011/218483
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author Leemann-Zakaryan, Ruzanna P.
Pahlich, Steffen
Grossenbacher, Doris
Gehring, Heinz
author_facet Leemann-Zakaryan, Ruzanna P.
Pahlich, Steffen
Grossenbacher, Doris
Gehring, Heinz
author_sort Leemann-Zakaryan, Ruzanna P.
collection PubMed
description Ewing sarcoma (EWS) proto-oncoprotein, an RNA-binding protein, is involved in DNA recombination and repair, gene expression, RNA processing and transport, as well as cell signalling. Chimeric EWS oncoproteins generated by chromosomal translocations between EWSR1 and the genes of transcription factors cause malignant tumors. To understand the loss of function by these translocations, the role of the intact EWS protein has to be investigated. The predominantly nuclear localization of the EWS protein via a transportin-1-mediated mechanism is dependent on the recently identified C-NLS (also known as PY-NLS). Among other residues in the C-NLS, Y656 interacts with transportin-1 and is essential for its nuclear localization. Here, we show that Y656 is phosphorylated, which seems to be a critical factor for transportin-1-mediated nuclear import. If Y656 was mutated cytosolic aggregates of the EWS protein, colocalized with transportin-1, were observed, similar to those described with mutants of the closely related FUS/TLS protein that had amino acid substitutions in the PY-NLS causing familial amyothrophic lateral sclerosis.
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spelling pubmed-31039762011-06-06 Tyrosine Phosphorylation in the C-Terminal Nuclear Localization and Retention Signal (C-NLS) of the EWS Protein Leemann-Zakaryan, Ruzanna P. Pahlich, Steffen Grossenbacher, Doris Gehring, Heinz Sarcoma Research Article Ewing sarcoma (EWS) proto-oncoprotein, an RNA-binding protein, is involved in DNA recombination and repair, gene expression, RNA processing and transport, as well as cell signalling. Chimeric EWS oncoproteins generated by chromosomal translocations between EWSR1 and the genes of transcription factors cause malignant tumors. To understand the loss of function by these translocations, the role of the intact EWS protein has to be investigated. The predominantly nuclear localization of the EWS protein via a transportin-1-mediated mechanism is dependent on the recently identified C-NLS (also known as PY-NLS). Among other residues in the C-NLS, Y656 interacts with transportin-1 and is essential for its nuclear localization. Here, we show that Y656 is phosphorylated, which seems to be a critical factor for transportin-1-mediated nuclear import. If Y656 was mutated cytosolic aggregates of the EWS protein, colocalized with transportin-1, were observed, similar to those described with mutants of the closely related FUS/TLS protein that had amino acid substitutions in the PY-NLS causing familial amyothrophic lateral sclerosis. Hindawi Publishing Corporation 2011 2011-05-02 /pmc/articles/PMC3103976/ /pubmed/21647358 http://dx.doi.org/10.1155/2011/218483 Text en Copyright © 2011 Ruzanna P. Leemann-Zakaryan et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Leemann-Zakaryan, Ruzanna P.
Pahlich, Steffen
Grossenbacher, Doris
Gehring, Heinz
Tyrosine Phosphorylation in the C-Terminal Nuclear Localization and Retention Signal (C-NLS) of the EWS Protein
title Tyrosine Phosphorylation in the C-Terminal Nuclear Localization and Retention Signal (C-NLS) of the EWS Protein
title_full Tyrosine Phosphorylation in the C-Terminal Nuclear Localization and Retention Signal (C-NLS) of the EWS Protein
title_fullStr Tyrosine Phosphorylation in the C-Terminal Nuclear Localization and Retention Signal (C-NLS) of the EWS Protein
title_full_unstemmed Tyrosine Phosphorylation in the C-Terminal Nuclear Localization and Retention Signal (C-NLS) of the EWS Protein
title_short Tyrosine Phosphorylation in the C-Terminal Nuclear Localization and Retention Signal (C-NLS) of the EWS Protein
title_sort tyrosine phosphorylation in the c-terminal nuclear localization and retention signal (c-nls) of the ews protein
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3103976/
https://www.ncbi.nlm.nih.gov/pubmed/21647358
http://dx.doi.org/10.1155/2011/218483
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