The PP2A-associated protein alpha4 is an essential inhibitor of apoptosis.
The PP2A-associated protein alpha4 is an essential inhibitor of apoptosis.
复制标题
PP2A 相关蛋白 α4 是细胞凋亡的重要抑制剂。
作者：
M. Kong;C. Fox;J. Mu;L. Solt;A. Xu;Ryan M. Cinalli;M. Birnbaum;T. Lindsten;C. Thompson
尽管有证据表明蛋白激酶是细胞凋亡的调节剂，但磷酸酶在调节细胞存活中的具体作用尚未确定。在这里，我们证明了蛋白磷酸酶2A （PP2A）的非催化亚基alpha4是抑制小鼠细胞凋亡所必需的。alpha4是转录因子c-Jun和p53去磷酸化的非冗余调节因子。由于alpha4缺失，多个促凋亡基因被转录。抑制新蛋白合成或Bcl-xL过表达均可抑制由alpha4缺失引发的细胞凋亡。因此，哺乳动物细胞活力依赖于PP2A成分介导的转录启动细胞凋亡的抑制。
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.