title: C-RAF activation promotes BAD poly-ubiquitylation and turn-over by the proteasome.
abstract: BAD, a member of the BCL2 family, exhibits an original mode of regulation by phosphorylation. In the present report, we examine the role of the kinase C-RAF in this process. We show that the inducible activation of C-RAF promotes the rapid phosphorylation of BAD on Serine-112 (Ser-75 in the human protein), through a cascade involving the kinases MEK and RSK. Our findings reveal a new aspect of the regulation of BAD protein and its control by the RAF pathway: we find that C-RAF activation promotes BAD poly-ubiquitylation in a phosphorylation-dependent fashion, and increases the turn-over of this protein through proteasomal degradation.
authors.affiliation: Institut für Medizinische Strahlenkunde und Zellforschung (MSZ), University of Würzburg, Versbacher Strasse 5, D-97078, Würzburg, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Fueller
authors.forename: Matthias
authors.initials: M
authors.lastname: Becker
authors.forename: Arnold R
authors.initials: AR
authors.lastname: Sienerth
authors.forename: Andreas
authors.initials: A
authors.lastname: Fischer
authors.forename: Christian
authors.initials: C
authors.lastname: Hotz
authors.forename: Antoine
authors.initials: A
authors.lastname: Galmiche
mesh_terms: D000818:Animals; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D025821:Polyubiquitin / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D054875:Ubiquitination; D051025:bcl-Associated Death Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: C494819:BAD protein, human; D051025:bcl-Associated Death Protein; D025821:Polyubiquitin; D012694:Serine; D019908:Proto-Oncogene Proteins c-raf; D046988:Proteasome Endopeptidase Complex