To the top

Page Manager: Webmaster
Last update: 9/11/2012 3:13 PM

Tell a friend about this page
Print version

A conserved N-terminal mo… - University of Gothenburg, Sweden Till startsida
Sitemap
To content Read more about how we use cookies on gu.se

A conserved N-terminal motif is required for complex formation between FUS, EWSR1, TAF15 and their oncogenic fusion proteins.

Journal article
Authors Christer Thomsen
Pernilla Grundevik
Per Elias
Anders Ståhlberg
Pierre Åman
Published in FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume 27
Issue 12
Pages 4965-74
ISSN 1530-6860
Publication year 2013
Published at Institute of Biomedicine, Department of Pathology
Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
Pages 4965-74
Language en
Links dx.doi.org/10.1096/fj.13-234435
Keywords Tumörgenetik
Subject categories Basic Medicine, Cell and molecular biology, Pathology, Molecular biology

Abstract

The three FET (FUS, EWSR1, and TAF15) family RNA binding proteins are expressed in all tissues and almost all cell types. The disordered N-terminal parts are always present in FET fusion oncoproteins of sarcomas and leukemia. Mutations in FUS and TAF15 cause aggregation of FET proteins in neurological disorders. Here we used recombinant proteins in pulldown experiments and mass spectrometry to identify major interaction partners of the FET N-terminal parts. We report that FUS, EWSR1, and TAF15 form homo- and heterocomplexes as major binding partners and identify an evolutionarily conserved N-terminal motif (FETBM1) that is required for this interaction. The binding is RNA and DNA independent and robust up to 1 M of NaCl. The localization of FETBM1 and its target sequences supports a simple model for FET protein aggregation as reported in neurological disorders such as amyotrophic lateral sclerosis, frontotemporal dementia, and essential tremor. The FETBM1 localization also explains the binding of normal full-length FET proteins to their oncogenic fusion proteins.-Thomsen, C., Grundevik, P., Elias, P., Ståhlberg, A., Åman, P. A conserved N-terminal motif is required for complex formation between FUS, EWSR1, TAF15 and their oncogenic fusion proteins.

Page Manager: Webmaster|Last update: 9/11/2012
Share:

The University of Gothenburg uses cookies to provide you with the best possible user experience. By continuing on this website, you approve of our use of cookies.  What are cookies?