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Science 306 (5696): 695-698

Copyright © 2004 by the American Association for the Advancement of Science

The PP2A-Associated Protein {alpha}4 Is an Essential Inhibitor of Apoptosis

Mei Kong,1,3 Casey J. Fox,1,3 James Mu,2 Laura Solt,1 Anne Xu,1,3 Ryan M. Cinalli,1,3 Morris J. Birnbaum,2 Tullia Lindsten,1,5 Craig B. Thompson1,3,4*

Abstract: 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 {alpha}4, a noncatalytic subunit of protein phosphatase 2A (PP2A), is required to repress apoptosis in murine cells. {alpha}4 is a nonredundant regulator of the dephosphorylation of the transcription factors c-Jun and p53. As a result of {alpha}4 deletion, multiple proapoptotic genes were transcribed. Either inhibition of new protein synthesis or Bcl-xL overexpression suppressed apoptosis initiated by {alpha}4 deletion. Thus, mammalian cell viability depends on repression of transcription-initiated apoptosis mediated by a component of PP2A.

1 Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
2 Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
3 Department of Cancer Biology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
4 Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
5 Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.

* To whom correspondence should be addressed. E-mail: craig{at}mail.med.upenn.edu


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