Inverse regulation of cyclin B1 by c-Myc and p53 and induction of tetraploidy by cyclin B1 overexpression.
Inverse regulation of cyclin B1 by c-Myc and p53 and induction of tetraploidy by cyclin B1 overexpression.
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发表时间：
2001-09
期刊：
影响因子：
11.2
通讯作者：
Xiao-ying Yin;L. Grove;N. Datta;K. Katula;M. Long;M. Long;E. Prochownik;E. Prochownik
中科院分区：
文献类型：
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作者：
Xiao-ying Yin;L. Grove;N. Datta;K. Katula;M. Long;M. Long;E. Prochownik;E. Prochownik
我们以前已经证明，有丝分裂纺锤体抑制剂允许c-MyconcoProtein将有丝分裂与DNA合成解偶联，导致获得四倍体。如果c-Myc去调控与p53肿瘤抑制基因失活相结合，在没有纺锤体抑制的情况下也可能发生这种情况。在这些条件下，Cyclin B1蛋白被诱导，但保持其正常的细胞周期调节。我们现在证明，细胞周期蛋白B1的启动子是由c-Myc和p53直接但相反地调节的。如果细胞周期蛋白B1与c-Myc共表达，则在有丝分裂纺锤体抑制后或在没有这种抑制的情况下，细胞周期蛋白B1的强制表达也会诱导四倍体。Cyclin B1代表了一类新的c-Myc靶基因，它也受P53的调控。它也是第一个被发现的c-Myc下游效应子，能够产生几乎所有肿瘤细胞都具有的染色体不稳定性。
We have shown previously that mitotic spindle inhibitors allow the c-Myconcoprotein to uncouple mitosis from DNA synthesis, resulting in the acquisition of tetraploidy. This can also occur in the absence of spindle inhibition if c-Myc deregulation is combined with inactivation of the p53 tumor suppressor. Under these conditions, cyclin B1 protein is induced but retains its normal cell cycle regulation. We now show that the cyclin B1 promoter is directly but oppositely regulated by c-Myc and p53. Enforced expression of cyclin B1 also induces tetraploidy, either after mitotic spindle inhibition or in the absence of such inhibition if cyclin B1 is coexpressed with c-Myc. Cyclin B1 represents a new class of c-Myc target genes that is also regulated by p53. It is also the first identified downstream effector of c-Myc able to produce the chromosomal instability that characterizes virtually all tumor cells.