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

BMC Cell Biology
|July 16, 2008
PubMed
Abstract

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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