CELL CYCLE REGULATION AND APOPTOSIS¹

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.