How does ERK1/2 signalling drive both cell proliferation and cell cycle arrest?

RAS-RAF-MEK-ERK1/2通路是一种众所周知的生长因子信号通路，它驱动细胞通过G1期进入细胞周期的S期，促进细胞分裂。它的关键方式是驱动d型细胞周期蛋白的表达，如细胞周期蛋白D1 (CCND1)，它激活细胞周期蛋白依赖性激酶4和6 （CDK4/6）。事实上，这一途径的解除调控会促进癌症中细胞分裂的解除调控。矛盾的是，ERK1/2信号也可以驱动细胞周期阻滞和分化，并且是正常发育过程中决定细胞命运的关键途径。激活相同的信号通路如何驱动如此明显相反的细胞命运？这个问题多年来一直困扰着细胞和发育生物学家，甚至困扰着他们。

The RAS-RAF-MEK-ERK1/2 pathway is well known as a growth factor signalling pathway that drives cells through G1 and into S phase of the cell cycle to promote cell division. Once critical way in which it does this is to drive expression of the D-type cyclins such as cyclin D1 (CCND1), which activate cyclin-dependent kinases 4 and 6 (CDK4/6). Indeed, de-regulation of this pathway promotes deregulated cell division in cancer. Paradoxically, ERK1/2 signalling can also drive cell cycle arrest and differentiation and is a critical pathway in cell fate determination during normal development. How can activation of the same signaling pathway drive such apparently opposing cell fates? This question has occupied - even vexed - cell and developmental biologists for many years.