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The CRAL/TRIO and GOLD domain protein TAP-1 regulates RAF-1 activation

Kenneth G Johnson1, Kerry Kornfeld

  • 1Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USA.

Developmental Biology
|March 17, 2010
PubMed

Insights

Alpha-tocopherol associated protein-1 (TAP-1) regulates Ras signaling by controlling Raf activation at the cell membrane. This conserved mechanism impacts cell division and cancer cell proliferation.

Area of Science:

  • Cellular biology
  • Molecular signaling
  • Developmental biology

Background:

  • Raf protein kinase activation at the cell membrane is crucial for cell signaling.
  • Mechanisms regulating Raf activity are not fully understood.
  • The C. elegans cgr-1 gene, encoding a CRAL/TRIO domain protein, modulates Ras-dependent cell fate.

Purpose of the Study:

  • Identify the mammalian functional ortholog of C. elegans cgr-1.
  • Investigate the role of the identified protein in Ras/ERK signaling.
  • Determine the mechanism by which this protein regulates Raf activity.

Main Methods:

  • Identification of mammalian ortholog using sequence homology.
  • Analysis of mRNA expression and protein localization.
  • RNA interference to reduce protein expression.
  • Biochemical assays to study protein interactions and signaling pathway modulation.

Main Results:

  • Mammalian alpha-tocopherol associated protein-1 (TAP-1) identified as a functional ortholog of cgr-1.
  • TAP-1 protein localizes with Ras and Raf at the cell membrane.
  • Reduced TAP-1 expression enhances Ras/ERK signaling.
  • TAP-1 negatively regulates Raf-1 recruitment to GTP-bound Ras.
  • Reduced TAP-1 expression increases the oncogenic potential of cancer cells.

Conclusions:

  • CRAL/TRIO domain proteins play a conserved role in regulating Ras signaling.
  • TAP-1 is a critical modulator of Ras-mediated cellular signaling.
  • TAP-1 influences cell division and has implications for cancer biology.

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