A conserved N-terminal motif is required for complex formation between FUS, EWSR1, TAF15 and their oncogenic fusion proteins.
FASEB J
; 27(12): 4965-74, 2013 Dec.
Article
in En
| MEDLINE
| ID: mdl-23975937
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.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Calmodulin-Binding Proteins
/
Oncogene Proteins, Fusion
/
RNA-Binding Proteins
/
RNA-Binding Protein FUS
/
TATA-Binding Protein Associated Factors
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
FASEB J
Journal subject:
BIOLOGIA
/
FISIOLOGIA
Year:
2013
Type:
Article
Affiliation country:
Sweden