The anti-apoptotic molecules Bcl-xL and Bcl-w target protein phosphatase 1alpha to Bad.
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.
Ayllón
Verónica
V
Centro Nacional de Biotenología, Department of Immunology and Oncology, Campus de Cantoblanco, UAM, Madrid, Spain.
Cayla
Xavier
X
García
Alphonse
A
Fleischer
Aarne
A
Rebollo
Angelita
A
D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D019319:Okadaic Acid / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054645:Protein Phosphatase 1; D011506:Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051025:bcl-Associated Death Protein; D051020:bcl-X Protein
D051017:Apoptosis Regulatory Proteins; C494819:BAD protein, human; C494811:BCL2L1 protein, human; C491073:BCL2L2 protein, human; C494820:Bad protein, mouse; C494812:Bcl2l1 protein, mouse; C101155:Bcl2l2 protein, mouse; D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051025:bcl-Associated Death Protein; D051020:bcl-X Protein; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1