Oncogenic serine-threonine kinase receptor-associated protein modulates the function of Ewing sarcoma protein through

Govindaraj Anumanthan1, Sunil K Halder, David B Friedman

  • 1Department of Surgery and Cancer Biology, Vanderbilt Ingram Cancer Center and Mass Spectrometry Research Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.

Cancer Research
|November 17, 2006
PubMed

Insights

Serine-threonine kinase receptor-associated protein (STRAP) interacts with the Ewing sarcoma (EWS) protein in the nucleus. STRAP inhibits EWS

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • The oncogenic functions of chimeric Ewing sarcoma (EWS) fusion proteins are known, but the role of normal EWS protein is unclear.
  • Serine-threonine kinase receptor-associated protein (STRAP) inhibits TGF-beta signaling and promotes tumor growth.
  • STRAP's interaction with EWS and its role in cancer require further investigation.

Purpose of the Study:

  • To investigate the interaction between STRAP and EWS.
  • To elucidate the functional consequences of this interaction in cancer.
  • To determine the mechanism by which STRAP regulates EWS function.

Main Methods:

  • Matrix-assisted laser desorption/ionization, time-of-flight, and tandem mass spectrometry were used to identify STRAP-EWS interaction.
  • Immunofluorescence and co-immunoprecipitation assays were employed to study protein localization and association.
  • Reporter gene assays were utilized to assess transcriptional activity.

Main Results:

  • STRAP and EWS interact in the nucleus, with STRAP binding to EWS through its NH(2) and COOH termini.
  • Normal EWS and STRAP are co-up-regulated in human colorectal and lung cancers.
  • STRAP inhibits EWS-dependent transactivation of target genes (ApoCIII, c-fos) by displacing the coactivator p300, independent of TGF-beta signaling.

Conclusions:

  • STRAP interacts with and regulates the function of normal EWS protein.
  • The STRAP-EWS interaction has implications for human cancers, suggesting a cooperative role.
  • STRAP inhibits EWS transactivation through a novel TGF-beta-independent mechanism involving p300 displacement.

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