Fibronectin controls cap-dependent translation through β1 integrin and eukaryotic initiation factors 4 and 2 coordinated pathways
Fibronectin controls cap-dependent translation through β1 integrin and eukaryotic initiation factors 4 and 2 coordinated pathways
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DOI：
10.1073/pnas.0409513102
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发表时间：
2005-06-28
影响因子：
11.1
通讯作者：
Biffo, S
中科院分区：
文献类型：
--
作者：
Gorrini, C;Loreni, F;Biffo, S
纤维连接蛋白（FN）是一种主要的基质蛋白，参与多种过程。很少有人知道如何粘附FN影响翻译机制。我们发现，在成纤维细胞粘附FN触发翻译通过协调调节真核起始因子（细胞）4F和2，并通过阻断β 1整合素参与受损。FN刺激的翻译具有独特的性质：（i）它对磷脂酰肌醇3-激酶（PI 3 K）的抑制高度敏感，但对PI 3 K下游的雷帕霉素哺乳动物靶点的抑制不敏感;（ii）血清刺激的翻译和FN依赖的翻译之间没有协同作用;（iii）与生长因子刺激的翻译不同，FN依赖的翻译不会导致5'末端寡嘧啶段mRNA向多核糖体的易位增加;和（iv）缺乏与基质附着的细胞显示伴随eIF 2 α磷酸化的翻译起始受损，其不能被活性PI 3 K逆转。这些发现表明，整合素可能以独特的方式招募翻译机器，FN依赖性翻译不能被哺乳动物靶向雷帕霉素抑制所阻断。
Fibronectin (FN) is a major matrix protein involved in multiple processes. Little is known about how adhesion to FN affects the translational machinery. We show that in fibroblasts adhesion to FN triggers translation through the coordinated regulation of eukaryotic initiation factors (ell's) 4F and 2 and is impaired by blocking beta 1 integrin engagement. FN-stimulated translation has unique properties: (i) it is highly sensitive to the inhibition of phosphaticlylinositol 3-kinase (PI3K), but not to the inhibition of mammalian target of rapamycin, downstream of PI3K; (ii) there is no synergy between serum-stimulated translation and FN-dependent translation; (iii) FN-dependent translation, unlike growth factor-stimulated translation, does not lead to increased translocation of 5' terminal oligopyrimidine tract mRNAs to polysomes; and (iv) cells devoid of attachment to matrix show an impairment of initiation of translation accompanied by phosphorylation of elF2 alpha, which cannot be reverted by active PI3K. These findings indicate that integrins may recruit the translational machinery in a unique way and that FN-dependent translation cannot be blocked by mammalian target of rapamycin inhibition.