Role of Bim in the survival pathway induced by Raf in epithelial cells
Role of Bim in the survival pathway induced by Raf in epithelial cells
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DOI：
10.1038/sj.onc.1207364
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发表时间：
2004-04-01
期刊：
影响因子：
8
通讯作者：
Lemoine, NR
中科院分区：
文献类型：
--
作者：
Marani, M;Hancock, D;Lemoine, NR
在MCF-10A DeltaRaf-ER细胞（一种自发永生化的人乳腺上皮细胞系）中，Raf/MAP激酶途径的选择性和持续激活先前显示可保护这些细胞免于悬浮诱导的细胞死亡，这是Ras转化表型的关键特征。虽然通过EGF受体的自分泌信号是至关重要的Raf诱导的保护在这些细胞中，我们在这里报告存在一个额外的，更直接的生存机制，连接Raf激活抑制Bcl-2家族的促凋亡成员，Bim。虽然从基质中分离导致该仅BH 3蛋白的两种变体BimEL和BimL的转录诱导，但Raf/ERK信号传导的激活既特异性地防止Bim上调，又导致BimEL同种型的磷酸化和降解。这代表了保护上皮细胞免受Bim促凋亡作用的重要途径。
Selective and sustained activation of the Raf/MAP kinase pathway in MCF-10A DeltaRaf-ER cells, a spontaneously immortalized human mammary epithelial cell line, was previously shown to protect these cells from suspension-induced cell death, a critical feature of the Ras-transformed phenotype. Although autocrine signalling through the EGF receptor is crucial for the protection induced by Raf in these cells, we report here the existence of an additional, more direct survival mechanism, linking Raf activation to the inhibition of a proapoptotic member of the Bcl-2 family, Bim. While detachment from the matrix results in transcriptional induction of two variants of this BH3-only protein, BimEL and BimL, activation of the Raf/ERK signalling both prevents Bim upregulation specifically and leads to phosphorylation and degradation of the BimEL isoform. This represents an important route to protect epithelial cells from the proapoptotic effect of Bim.