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The multifunctional FUS, EWS and TAF15 proto-oncoproteins show cell type-specific expression patterns and involvement
Mattias K Andersson1, Anders Ståhlberg, Yvonne Arvidsson
1Lundberg Laboratory for Cancer Research, Department of Pathology, Sahlgrenska Academy at Göteborg University, Göteborg, Sweden. mattias.andersson@llcr.med.gu.se
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.
Insights
The FET (FUS, EWS, TAF15) proteins show varied expression across human tissues and cell types. Their localization to stress granules suggests roles in translational control and cancer, challenging previous assumptions of housekeeping functions.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- The FET (FUS, EWS, TAF15) proteins are multifunctional RNA-binding proteins involved in gene expression, genomic integrity, and RNA processing.
- These proteins were initially identified in human sarcoma and leukemia fusion oncogenes.
Purpose of the Study:
- To investigate the expression patterns and cellular localization of FET proteins in various human tissues and cell types.
- To understand the functional implications of FET protein localization, particularly under stress conditions.
Main Methods:
- Analysis of FET protein expression across multiple human tissues.
- Examination of FET protein localization in different cell types, including differentiating and terminally differentiated cells.
- Induction of stress conditions (heat shock, oxidative stress) to observe FET protein translocation to stress granules.
- Investigation of FUS protein translocation mechanism using its RNA-binding domain.
- Detection of FET proteins in spreading initiation centers of adhering cells.
Main Results:
- FET proteins (FUS, EWS, TAF15) exhibit distinct and overlapping expression patterns in human tissues, primarily in the nucleus.
- FUS and TAF15 are also found in the cytoplasm, while cytoplasmic EWS is rarer and observed in secretory cells.
- FET expression decreases during cellular differentiation and is absent in terminally differentiated cells.
- FET proteins translocate to stress granules under heat shock and oxidative stress; FUS translocation depends on its RNA-binding domain.
- FUS and TAF15 are present in spreading initiation centers, indicating roles in cell adhesion.
Conclusions:
- FET proteins display cell-specific expression and functions, diverging from previously inferred housekeeping roles.
- Localization to stress granules suggests FET proteins are involved in translational regulation during cellular stress.
- The involvement of FET proteins in stress response, translational control, and adhesion may explain their frequent association with human cancers.
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