Mip/LIN-9 regulates the expression of B-Myb and the induction of cyclin A, cyclin B, and CDK1
Mip/LIN-9 regulates the expression of B-Myb and the induction of cyclin A, cyclin B, and CDK1
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DOI：
10.1074/jbc.m609924200
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发表时间：
2007-01-05
影响因子：
4.8
通讯作者：
Colamonici, Oscar R.
中科院分区：
文献类型：
--
作者：
Pilkinton, Mark;Sandoval, Raudel;Colamonici, Oscar R.
新蛋白家族的成员包括果蝇Mip130、秀丽隐杆线虫LIN-9和哺乳动物LIN-9，它们干预不同的细胞功能，如转录、分化、转化和细胞周期进程的调节。在这里，我们证明LIN-9，被称为Mip/LIN-9，与B-Myb相互作用，但不与c-Myb或A-Myb相互作用。Mip/LIN-9通过转录后方式调控B- myb的表达，其缺失不仅会降低B- myb蛋白的水平，还会影响S期和有丝分裂基因（即细胞周期蛋白a、CDK1和细胞周期蛋白B）的表达。Mip/LIN-9和B- myb的共表达可激活细胞周期蛋白A和细胞周期蛋白B启动子-荧光素酶报告子，并且在细胞周期蛋白A和B启动子上检测到这两种蛋白，这一发现进一步支持了Mip/LIN-9对S和G(2)/M基因表达的关键作用。有趣的是，尽管Mip/ LIN-9启动子占用高峰早于B- myb，但细胞周期蛋白A和B的最高表达水平与B- myb与这些启动子的最大结合相关。这些数据支持了Mip/LIN-9是B-Myb表达所必需的概念，并且这两种蛋白通过调控S期和有丝分裂周期蛋白共同控制细胞周期进程。
Members of the novel family of proteins that include Drosophila Mip130, Caenorhabditis elegans LIN-9, and mammalian LIN-9 intervene in different cellular functions such as regulation of transcription, differentiation, transformation, and cell cycle progression. Here we demonstrate that LIN-9, designated as Mip/LIN-9, interacts with B-Myb but not with c-Myb or A-Myb. Mip/LIN-9 regulates the expression of B-Myb in a post-transcriptional manner, and its depletion not only decreases the level of the B-Myb protein but also affects the expression of S phase and mitotic genes (i.e. cyclin A, CDK1, and cyclin B). The critical role of Mip/LIN-9 on the expression of S and G(2)/M genes is further supported by the finding that coexpression of Mip/ LIN-9 and B-Myb results in the activation of cyclin A and cyclin B promoter-luciferase reporters, and both proteins are detected on the cyclin A and B promoters. Interestingly, although Mip/ LIN-9 promoter occupancy peaks earlier than B-Myb, the highest levels of expression of cyclins A and B correlate with the maximum binding of B-Myb to these promoters. These data support the concept that Mip/LIN-9 is required for the expression of B-Myb, and both proteins collaborate in the control of the cell cycle progression via the regulation of S phase and mitotic cyclins.