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The PP2A-Associated Protein 4 Is an Essential Inhibitor of Apoptosis
Mei Kong,1,3Casey J. Fox,1,3James Mu,2Laura Solt,1Anne Xu,1,3Ryan M. Cinalli,1,3Morris J. Birnbaum,2Tullia Lindsten,1,5Craig B. Thompson1,3,4*
Despite evidence that protein kinases are regulators of apoptosis,a specific role for phosphatases in regulating cell survivalhas not been established. Here we show that 4, a noncatalyticsubunit of protein phosphatase 2A (PP2A), is required to repressapoptosis in murine cells. 4 is a nonredundant regulator ofthe dephosphorylation of the transcription factors c-Jun andp53. As a result of 4 deletion, multiple proapoptotic geneswere transcribed. Either inhibition of new protein synthesisor Bcl-xL overexpression suppressed apoptosis initiated by 4deletion. Thus, mammalian cell viability depends on repressionof transcription-initiated apoptosis mediated by a componentof 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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4 Is an Essential Inhibitor of Apoptosis
4, a noncatalytic subunit of protein phosphatase 2A (PP2A), is required to repress apoptosis in murine cells. 
