Blagosklonny M V
Medicine Branch, National Cancer Institute, Bldg. 10, R 12N226, NIH, Bethesda, Maryland 20892, USA.
Bioessays. 1999 Aug;21(8):704-9. doi: 10.1002/(SICI)1521-1878(199908)21:8<704::AID-BIES10>3.0.CO;2-5.
Paradoxically, oncogenes and growth factors can induce proliferation and promote cellular survival but can also cause apoptosis and growth arrest. What determines whether a cell decides to proliferate, arrest growth, or die? Mitogens and activators of mitogen-activated pathways initiate the simultaneous production of proliferative (cyclins) and anti-proliferative (CDK inhibitors such as p21WAF1/CIP1) signals. Quiescent cells may respond to these signals by proliferation whereas proliferating cells may respond by growth arrest. Although pro-apoptotic oncoproteins, which constitute the downstream pathway (cyclin D, E2F, c-myc) directly induce proliferation, the activation of the upstream steps (growth factor receptors, Ras, cytoplasmic kinases) is required to prevent apoptosis.
矛盾的是，癌基因和生长因子既能诱导细胞增殖并促进细胞存活，也能导致细胞凋亡和生长停滞。是什么决定了细胞是决定增殖、停止生长还是死亡呢？有丝分裂原和丝裂原激活途径的激活剂会同时启动增殖信号（细胞周期蛋白）和抗增殖信号（如p21WAF1/CIP1等细胞周期蛋白依赖性激酶抑制剂）的产生。静止细胞可能通过增殖对这些信号作出反应，而增殖细胞可能通过生长停滞作出反应。尽管构成下游途径（细胞周期蛋白D、E2F、c-myc）的促凋亡癌蛋白直接诱导增殖，但需要上游步骤（生长因子受体、Ras、细胞质激酶）的激活来防止细胞凋亡。
