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.