Manipulating the onset of cell cycle withdrawal in differentiated erythroid cells with cyclin-dependent kinases and inhibitors
Manipulating the onset of cell cycle withdrawal in differentiated erythroid cells with cyclin-dependent kinases and inhibitors
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DOI：
10.1182/blood.v96.8.2755.h8002755_2755_2764
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发表时间：
2000-10-15
期刊：
影响因子：
20.3
通讯作者：
Skoultchi, AI
中科院分区：
文献类型：
--
作者：
Matushansky, I;Radparvar, F;Skoultchi, AI
红系细胞的终末分化导致终末细胞分裂，随后是血红蛋白化细胞的不可逆细胞周期退出。在小鼠红白血病细胞的稳定转染子中评估导致细胞周期退出的机制，其中细胞周期蛋白依赖性激酶（CDK）和CDK抑制剂（CDKI）的活性在分化期间可以被严格调节。分化细胞的细胞周期退出由几种CDKIs的诱导介导，从而导致CDK2和CDK4的抑制。分化细胞中CDK活性的操纵表明，细胞周期退出的开始可以大大加速或大大延迟，而不影响血红蛋白水平。延长分化细胞的增殖需要CDK2和CDK4的协同作用，重要的是，CDK6不能替代CDK4在这一作用中，这表明2种细胞周期蛋白D依赖性激酶在功能上不同。结果表明，可以使分化的血红蛋白化细胞增殖远远超过其正常分裂能力。(C)2000年，美国血液学会。
Terminal differentiation of erythroid cells results in terminal cell divisions followed by irreversible cell cycle withdrawal of hemoglobinized cells. The mechanisms leading to cell cycle withdrawal were assessed in stable transfectants of murine erythroleukemia cells, in which the activities of cyclin-dependent kinases (CDKs) and CDK inhibitors (CDKIs) could be tightly regulated during differentiation. Cell cycle withdrawal of differentiating cells is mediated by induction of several CDKIs, thereby leading to inhibition of CDK2 and CDK4, Manipulation of CDK activity in differentiating cells demonstrates that the onset of cell cycle withdrawal can be either greatly accelerated or greatly delayed without affecting hemoglobin levels. Extending the proliferation of differentiating cells requires the synergistic action of CDK2 and CDK4, Importantly, CDK6 cannot substitute for CDK4 in this role, which demonstrates that the 2 cyclin D-dependent kinases are functionally different. The results show that differentiating hemoglobinized cells can be made to proliferate far beyond their normal capacity to divide. (C) 2000 by The American Society of Hematology.