TGF-β inhibits p70 S6 kinase via protein phosphatase 2A to induce G1 arrest
TGF-β inhibits p70 S6 kinase via protein phosphatase 2A to induce G1 arrest
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DOI：
10.1101/gad.854200
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发表时间：
2000-12-15
影响因子：
10.5
通讯作者：
Oft, M
中科院分区：
文献类型：
--
作者：
Petritsch, C;Beug, H;Oft, M
在与转化生长因子-β结合时，转化生长因子-β受体直接磷酸化并激活转录因子Smad2/3，导致G(1)期停滞。在这里，我们提出了第二个平行的，依赖于转化生长因子-β的细胞周期停滞途径的证据，通过抑制p70(S6K)实现。转化生长因子-β诱导其受体与蛋白磷酸酶-2A(PP2A)-Bα结合。同时，三个PP2A亚基Bα、Aβ和Cα与p70(S6K)相关联，导致其去磷酸化和失活。尽管这两种途径都足以引起G(1)期停滞，但通过抑制p70(S6K)和通过Smad蛋白转录来释放转化生长因子-β诱导的G(1)期停滞需要抑制p70(S6K)。因此，转化生长因子-β调节细胞周期进程的翻译和转录后控制。
On TGF-beta binding, the TGF-beta receptor directly phosphorylates and activates the transcription factors Smad2/3, leading to G(1) arrest. Here, we present evidence for a second, parallel, TGF-beta -dependent pathway for cell cycle arrest, achieved via inhibition of p70(s6k). TGF-beta induces association of its receptor with protein phosphatase-2A (PP2A)-B alpha. Concomitantly, three PP2A-subunits, B alpha, A beta, and C alpha, associate with p70(s6k), leading to its dephosphorylation and inactivation. Although either pathway is sufficient to induce G(1) arrest, abrogation of both, the inhibition of p70(s6k), and transcription through Smad proteins is required for release of epithelial cells from TGF-beta -induced G(1) arrest. TGF-beta thereby modulates the translational and posttranscriptional control of cell cycle progression.