Pilkinton Mark, Sandoval Raudel, Song Julie, Ness Scott A, Colamonici Oscar R
Department of Pharmacology, University of Illinois, Chicago, Illinois 60612, USA.
J Biol Chem. 2007 Jan 5;282(1):168-75. doi: 10.1074/jbc.M609924200. Epub 2006 Nov 10.
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.
包含果蝇Mip130、秀丽隐杆线虫LIN-9和哺乳动物LIN-9的新型蛋白质家族成员参与不同的细胞功能，如转录调控、分化、转化和细胞周期进程。在此，我们证明被命名为Mip/LIN-9的LIN-9与B-Myb相互作用，但不与c-Myb或A-Myb相互作用。Mip/LIN-9以转录后方式调节B-Myb的表达，其缺失不仅降低B-Myb蛋白水平，还影响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与B-Myb共表达导致细胞周期蛋白A和细胞周期蛋白B启动子-荧光素酶报告基因激活，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期和G(2)/M期基因表达的关键作用。有趣的是，尽管Mip/LIN-9对启动子的占据早于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表达所必需的这一概念，并且这两种蛋白通过调节S期和有丝分裂细胞周期蛋白共同控制细胞周期进程。
