The PP2A-Associated Protein α4 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 α 4, a noncatalytic subunit of protein phosphatase 2A (PP2A), is required to repress apoptosis in murine cells. α 4 is a nonredu...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2004-10, Vol.306 (5696), p.695-698
Main Authors: Kong, Mei, Fox, Casey J., Mu, James, Solt, Laura, Xu, Anne, Cinalli, Ryan M., Birnbaum, Morris J., Lindsten, Tullia, Thompson, Craig B.
Format: Article
Language:English
Subjects:
Adipocytes
Ageing, cell death
Alleles
Antibodies
Apoptosis
Biological and medical sciences
Cell death
Cell lines
Cell physiology
Cellular control mechanisms
Cellular immunity
Fundamental and applied biological sciences. Psychology
Genetic aspects
Infections
Mice
Molecular and cellular biology
Physiological aspects
T lymphocytes
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Summary: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 α 4, a noncatalytic subunit of protein phosphatase 2A (PP2A), is required to repress apoptosis in murine cells. α 4 is a nonredundant regulator of the dephosphorylation of the transcription factors c-Jun and p53. As a result of α 4 deletion, multiple proapoptotic genes were transcribed. Either inhibition of new protein synthesis or Bcl-xLoverexpression suppressed apoptosis initiated by α 4 deletion. Thus, mammalian cell viability depends on repression of transcription-initiated apoptosis mediated by a component of PP2A.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1100537