Cdc25A stability is controlled by the ubiquitin-proteasome pathway during cell cycle progression and terminal differentiation
Cdc25A stability is controlled by the ubiquitin-proteasome pathway during cell cycle progression and terminal differentiation
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DOI：
10.1038/sj.onc.1203564
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发表时间：
2000-05-11
期刊：
影响因子：
8
通讯作者：
Hoffman, B
中科院分区：
文献类型：
--
作者：
Bernardi, R;Liebermann, DA;Hoffman, B
cdc25家族的成员是在细胞周期进程中起关键作用的蛋白磷酸酶。Cdc25A已被证明是哺乳动物细胞G1/S转变的关键调节因子，并且是具有致癌特性的myc靶基因。我们研究了cdc25A在髓母细胞白血病M1细胞终末分化过程中的调控作用，该细胞可通过白细胞介素-6 （IL-6）治疗诱导分化为巨噬细胞。在本报告中，我们发现cdc25A蛋白在终末分化和循环细胞中都被泛素-蛋白酶体机制降解。Cdc25A在细胞周期进程中有两个主要的积累峰，一个在G1期，另一个在S/G2期。有证据表明，在终末分化的髓细胞中，与循环细胞相比，泛素-蛋白酶体机制对Cdc25A的降解加速。此外，在M1细胞中，c-myc的表达失调，之前被证明可以阻止终末分化，也被发现可以阻止IL-6诱导的Cdc25A的降解。
Members of the cdc25 family are protein phosphatases that play pivotal roles in cell cycle progression. Cdc25A has been shown to be a critical regulator of the G1/S transition of mammalian cells and to be a myc-target gene with oncongenic properties. We investigated the regulation of cdc25A during terminal differentiation using myeloblastic leukemia M1 cells, that can be induced to undergo differentiation into macrophages by interleukin-6 (IL-6) treatment. In this report it is shown that cdc25A protein is degraded by the ubiquitin-proteasome machinery in both terminally differentiating and cycling cells. Cdc25A was found to have two major peaks of accumulation during cell cycle progression, one in G1 and the other in S/G2, Evidence was obtained that degradation of cdc25A by the ubiquitin-proteasome machinery in terminally differentiating myeloid cells is accelerated compared to cycling cells, Moreover, deregulated expression of c-myc in M1 cells, which had been previously shown to block terminal differentiation, was also found to block IL-6 induced degradation of cdc25A.