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C-RAF activation promotes BAD poly-ubiquitylation and turn-over by the proteasome

Jochen Fueller1, Matthias Becker, Arnold R Sienerth

  • 1Institut für Medizinische Strahlenkunde und Zellforschung (MSZ), University of Würzburg, Versbacher Strasse 5, D-97078, Würzburg, Germany.

Biochemical and Biophysical Research Communications
|April 12, 2008
PubMed

Insights

The RAF pathway, involving C-RAF kinase, regulates BAD protein phosphorylation and degradation. C-RAF activation leads to BAD poly-ubiquitylation and proteasomal turnover.

Area of Science:

  • Cellular biology
  • Molecular mechanisms of protein regulation

Background:

  • BAD is a BCL2 family member involved in apoptosis.
  • Protein phosphorylation is a key regulatory mechanism.

Purpose of the Study:

  • To investigate the role of C-RAF kinase in BAD protein regulation.
  • To elucidate the signaling cascade involved in BAD phosphorylation.

Main Methods:

  • Inducible activation of C-RAF kinase.
  • Analysis of BAD protein phosphorylation at Serine-112.
  • Investigation of downstream signaling pathways (MEK, RSK).
  • Assessment of BAD poly-ubiquitylation and proteasomal degradation.

Main Results:

  • C-RAF activation rapidly phosphorylates BAD on Serine-112 via MEK and RSK.
  • Phosphorylation-dependent BAD poly-ubiquitylation is induced by C-RAF.
  • C-RAF activation increases BAD protein turnover through proteasomal degradation.

Conclusions:

  • C-RAF is a novel regulator of BAD protein.
  • The RAF/MEK/RSK pathway controls BAD phosphorylation and subsequent degradation.
  • This pathway offers new insights into the regulation of apoptosis.

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