King K L, Cidlowski J A
Department of Molecular and Cellular Physiology, University of Cincinnati Medical Center, Ohio 45267-0576, USA.
Annu Rev Physiol. 1998;60:601-17. doi: 10.1146/annurev.physiol.60.1.601.
Tissue homeostasis requires a balance between cell proliferation and death. Apoptosis and proliferation are linked by cell cycle regulators, and apoptotic stimuli affect both cell proliferation and death. Glucocorticoids induce G1 arrest and apoptosis in transformed lymphoid cells. Decreased expression of the cell cycle components c-myc and cyclin D3 is essential for glucocorticoid-induced growth arrest and death in dividing cells. Other G1 regulators, such as p53, pRb, and E2F, have also been implicated in apoptosis. Mice lacking either p53 or E2F display aberrant cell proliferation and tumor formation, suggesting that these proteins are involved in the elimination of abnormal cells through apoptosis. In contrast, pRb induces G1 arrest and suppresses apoptosis in cultured cells. Mice that lack pRb are nonviable and show ectopic mitosis and massive cell death, suggesting that pRb is an apoptotic suppressor. Further analysis of common components of apoptotic and cell cycle machinery may provide insight into the coordinated regulation of these antagonistic processes.
组织稳态需要细胞增殖与死亡之间的平衡。细胞凋亡和增殖通过细胞周期调节因子相互关联，凋亡刺激会影响细胞增殖和死亡。糖皮质激素可诱导转化的淋巴细胞发生G1期阻滞和凋亡。细胞周期成分c-myc和细胞周期蛋白D3表达的降低对于糖皮质激素诱导的分裂细胞生长阻滞和死亡至关重要。其他G1期调节因子，如p53、pRb和E2F，也与细胞凋亡有关。缺乏p53或E2F的小鼠表现出异常的细胞增殖和肿瘤形成，这表明这些蛋白质参与通过细胞凋亡清除异常细胞。相反，pRb可诱导G1期阻滞并抑制培养细胞中的凋亡。缺乏pRb的小鼠无法存活，并表现出异位有丝分裂和大量细胞死亡，这表明pRb是一种凋亡抑制因子。对凋亡和细胞周期机制共同成分的进一步分析可能有助于深入了解这些拮抗过程的协调调节。
