The anti-apoptotic molecules Bcl-xL and Bcl-w target protein phosphatase 1α to Bad

✍ Scribed by Verónica Ayllón; Xavier Cayla; Alphonse García; Aarne Fleischer; Angelita Rebollo

• Book ID: 101379959
• Publisher: John Wiley and Sons
• Year: 2002
• Tongue: English
• Weight: 334 KB
• Volume: 32
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/1521-4141(200207)32:7<1847::aid-immu1847>3.0.co;2-7

✦ Synopsis

Bcl-xL and Bcl-w specifically interact with PP1alpha and Bad. A phosphatase activity sensitive to okadaic acid was detected in Bcl-xL, Bcl-w and Bad immunoprecipitates. Serine phosphorylation of Bcl-xL and Bcl-w correlates with the number of trimolecular complexes formed. Depletion of Bcl-xL and Bcl-w decreases the remaining Bad-associated phosphatase activity and association of protein phosphatase 1 (PP1)alpha to Bad. Bcl-xL and Bcl-w contain the R/K X V/I X F consensus motif shared by PP1 targeting subunits. This motif, in addition to F X X R X R motif, is involved in binding of Bcl-xL and Bcl-w to PP1alpha. Disruption of Bcl-xL/PP1alpha or Bcl-w/PP1alpha association strongly decreases Bad-associated phosphataseactivity and stability of trimolecular complexes. These results suggest that Bcl-xL and Bcl-w are PP1alpha targeting subunits and this trimolecular complex may be involved in the control of apoptosis.