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The multifunctional FUS, EWS and TAF15 proto-oncoproteins show cell type-specific expression patterns and involvement in cell spreading and stress response

Journal article
Authors Mattias K Andersson
Anders Ståhlberg
Yvonne Arvidsson
Anita Olofsson
Henrik Semb
Göran Stenman
Ola Nilsson
Pierre Åman
Published in BMC Cell Biology
Volume 9
Pages 37
ISSN 1471-2121
Publication year 2008
Published at Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation
Institute of Biomedicine, Department of Pathology
Pages 37
Language en
Links dx.doi.org/10.1186/1471-2121-9-37
Keywords Cell Adhesion/*genetics, Cell Shape, Gene Expression Regulation/*physiology, Heat-Shock Response, Humans, Oncogene Proteins/*genetics, Oxidative Stress/*genetics, RNA-Binding Protein EWS/genetics, RNA-Binding Protein FUS/genetics, TATA-Binding Protein Associated Factors/genetics
Subject categories Pathology

Abstract

BACKGROUND: FUS, EWS and TAF15 are structurally similar multifunctional proteins that were first discovered upon characterization of fusion oncogenes in human sarcomas and leukemias. The proteins belong to the FET (previously TET) family of RNA-binding proteins and are implicated in central cellular processes such as regulation of gene expression, maintenance of genomic integrity and mRNA/microRNA processing. In the present study, we investigated the expression and cellular localization of FET proteins in multiple human tissues and cell types. RESULTS: FUS, EWS and TAF15 were expressed in both distinct and overlapping patterns in human tissues. The three proteins showed almost ubiquitous nuclear expression and FUS and TAF15 were in addition present in the cytoplasm of most cell types. Cytoplasmic EWS was more rarely detected and seen mainly in secretory cell types. Furthermore, FET expression was downregulated in differentiating human embryonic stem cells, during induced differentiation of neuroblastoma cells and absent in terminally differentiated melanocytes and cardiac muscle cells. The FET proteins were targeted to stress granules induced by heat shock and oxidative stress and FUS required its RNA-binding domain for this translocation. Furthermore, FUS and TAF15 were detected in spreading initiation centers of adhering cells. CONCLUSION: Our results point to cell-specific expression patterns and functions of the FET proteins rather than the housekeeping roles inferred from earlier studies. The localization of FET proteins to stress granules suggests activities in translational regulation during stress conditions. Roles in central processes such as stress response, translational control and adhesion may explain the FET proteins frequent involvement in human cancer.

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