Biologie Moléculaire et Cellulaire de la Signalisation, EA 3919, UFR de médecine, IFR 146, Université de Caen, Caen, France.
Cancer Res. 2011 Mar 1;71(5):1690-9. doi: 10.1158/0008-5472.CAN-10-2564. Epub 2011 Feb 22.
Cyclin D1 is a cell cycle regulatory protein that acts at the G1-S transition, following its binding to and activation by the cyclin-dependent kinases 4 or 6. Cyclin D1 is absent from the entire B-cell lineage but is present in a large percentage of 2 types of malignant B-cell hemopathy--mantle cell lymphoma and multiple myeloma--suggesting a major role of this protein in the malignancy process. We show here, in an experimental model of cyclin D1 fusion protein transduction in mature B cells, that, cyclin D1 inhibits total mitochondrial activity. Cyclin D1 is localized at the outer mitochondrial membrane, bound to a voltage-dependent anion channel through its central domain, and it competes with hexokinase 2 for binding to this channel. The bound cyclin D1 decreases the supply of ADP, ATP, and metabolites, thereby reducing energy production. This function of cyclin D1 was also reported by others in normal and transformed mammary epithelial cells, suggesting that it may be ubiquitous.
周期蛋白 D1 是一种细胞周期调节蛋白，在 G1-S 转换时起作用，其通过与细胞周期蛋白依赖性激酶 4 或 6 结合并被其激活。周期蛋白 D1 不存在于整个 B 细胞谱系中，但存在于两种恶性 B 细胞血液病——套细胞淋巴瘤和多发性骨髓瘤——中，这表明该蛋白在恶性肿瘤过程中起主要作用。我们在这里的一个成熟 B 细胞中周期蛋白 D1 融合蛋白转导的实验模型中表明，周期蛋白 D1 抑制总线粒体活性。周期蛋白 D1 位于外线粒体膜上，通过其中心结构域与电压依赖性阴离子通道结合，并与己糖激酶 2 竞争与该通道的结合。结合的周期蛋白 D1 减少了 ADP、ATP 和代谢物的供应，从而减少了能量的产生。其他研究人员在正常和转化的乳腺上皮细胞中也报道了周期蛋白 D1 的这一功能，表明它可能是普遍存在的。
