Publication Date:
2004-10-23
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kong, Mei -- Fox, Casey J -- Mu, James -- Solt, Laura -- Xu, Anne -- Cinalli, Ryan M -- Birnbaum, Morris J -- Lindsten, Tullia -- Thompson, Craig B -- New York, N.Y. -- Science. 2004 Oct 22;306(5696):695-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15499020" target="_blank"〉PubMed〈/a〉
Keywords:
Adipocytes/cytology
;
Animals
;
*Apoptosis
;
Cell Differentiation
;
Cell Line
;
Cell Survival
;
Cells, Cultured
;
Cycloheximide/pharmacology
;
Gene Deletion
;
Gene Expression Profiling
;
Liver/cytology/metabolism
;
Mice
;
Mice, Transgenic
;
Oligonucleotide Array Sequence Analysis
;
PPAR gamma/metabolism
;
Phosphoprotein Phosphatases/*metabolism
;
Phosphoproteins/*metabolism
;
Phosphorylation
;
Protein Phosphatase 2
;
Protein Synthesis Inhibitors/pharmacology
;
Proto-Oncogene Proteins c-bcl-2/metabolism
;
Proto-Oncogene Proteins c-jun/metabolism
;
Transcription, Genetic
;
Tumor Suppressor Protein p53/metabolism
;
bcl-X Protein
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
