The PP2A-associated protein alpha4 is an essential inhibitor of apoptosis.
Despite evidence that protein kinases are regulators of apoptosis, a specific role for phosphatases in regulating cell survival has not been established. Here we show that alpha4, a noncatalytic subunit of protein phosphatase 2A (PP2A), is required to repress apoptosis in murine cells. alpha4 is a nonredundant regulator of the dephosphorylation of the transcription factors c-Jun and p53. As a result of alpha4 deletion, multiple proapoptotic genes were transcribed. Either inhibition of new protein synthesis or Bcl-xL overexpression suppressed apoptosis initiated by alpha4 deletion. Thus, mammalian cell viability depends on repression of transcription-initiated apoptosis mediated by a component of PP2A.
Kong
Mei
M
Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
Fox
Casey J
CJ
Mu
James
J
Solt
Laura
L
Xu
Anne
A
Cinalli
Ryan M
RM
Birnbaum
Morris J
MJ
Lindsten
Tullia
T
Thompson
Craig B
CB
D048868:Adaptor Proteins, Signal Transducing; D017667:Adipocytes / Q000166:cytology; D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D002460:Cell Line; D002470:Cell Survival; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D017353:Gene Deletion; D020869:Gene Expression Profiling; D036341:Intercellular Signaling Peptides and Proteins; D008099:Liver / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D018832:Molecular Chaperones; D020411:Oligonucleotide Array Sequence Analysis; D047495:PPAR gamma / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D054648:Protein Phosphatase 2; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051020:bcl-X Protein
D048868:Adaptor Proteins, Signal Transducing; C494812:Bcl2l1 protein, mouse; C092377:Igbp1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; D047495:PPAR gamma; D010750:Phosphoproteins; D011500:Protein Synthesis Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D016755:Proto-Oncogene Proteins c-jun; D016159:Tumor Suppressor Protein p53; D051020:bcl-X Protein; D003513:Cycloheximide; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2