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Expression of raf oncogenes activates the PEA1 transcription factor motif

C Wasylyk1, B Wasylyk, G Heidecker

  • 1Laboratoire de Génétique Moléculaire des Eucaryotes, Unité 184 Institut National de la Santé et de la Recherche Médicale, Faculté de Médecine, Strasbourg, France.

Molecular and Cellular Biology
|May 1, 1989
PubMed

Insights

Transcription enhancer PEA1 (AP1) activity is boosted by v-raf and activated c-raf-1/A-raf, suggesting a role in raf-mediated transformation. ATP-binding site mutations in v-raf blocked activation, indicating phosphorylation is necessary.

Area of Science:

  • Molecular biology
  • Cell signaling
  • Oncogenesis

Background:

  • The PEA1 (AP1) motif is a regulatory element involved in gene transcription.
  • Raf proteins are key components of signaling pathways implicated in cell growth and transformation.

Purpose of the Study:

  • To investigate the role of PEA1 transcription enhancer activity in raf-mediated cellular transformation.
  • To determine the impact of different raf forms and mutations on PEA1 activity.

Main Methods:

  • Assessing PEA1 transcription enhancer activity in response to various raf constructs.
  • Utilizing site-directed mutagenesis to probe the function of the ATP-binding site in v-raf.

Main Results:

  • v-raf, activated c-raf-1, and A-raf significantly stimulated PEA1 transcription enhancer activity.
  • Activated raf forms were more potent stimulators than their normal counterparts.
  • Mutations within the ATP-binding site of v-raf abolished its ability to activate PEA1.

Conclusions:

  • PEA1 plays a role in cellular transformation mediated by raf proteins.
  • Phosphorylation, likely dependent on the ATP-binding site, is essential for raf-mediated activation of PEA1.

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