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

RAS-RAF-MEK-ERK 1/2通路是众所周知的生长因子信号通路，其驱动细胞通过细胞周期的G1期并进入S期以促进细胞分裂。一个关键的方式是驱动D型细胞周期蛋白的表达，如细胞周期蛋白D1（CCND 1），它激活细胞周期蛋白依赖性激酶4和6（CDK 4/6）。事实上，该途径的失调促进癌症中失调的细胞分裂。巧合的是，ERK 1/2信号也可以驱动细胞周期停滞和分化，并且是正常发育期间细胞命运决定的关键途径。相同信号通路的激活如何驱动如此明显相反的细胞命运？这个问题已经困扰了细胞和发育生物学家很多年，甚至让他们感到烦恼。

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.