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.
Centro Nacional de Biotenología, Department of Immunology and Oncology, Campus de Cantoblanco, UAM, Madrid, Spain.
Verónica
V
Ayllón
Xavier
X
Cayla
Alphonse
A
García
Aarne
A
Fleischer
Angelita
A
Rebollo
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