Schneider G, Reichert M, Saur D, Hamacher R, Fritsch R, Schmid R M
Department of Internal Medicine II, Technical University of Munich, Munich, Germany.
Cell Prolif. 2007 Aug;40(4):522-31. doi: 10.1111/j.1365-2184.2007.00454.x.
Histone deacetylases (HDACs) have been linked to cell cycle control in various models, involving regulation of the cyclin-dependent kinase inhibitor p27(Kip1).
Here, we demonstrate that HDAC inhibition by trichostatin A reduces S-phase kinase-associated protein 2 mRNA and protein abundance. Furthermore, in contrast to HDAC1, recruited to the skp2 promoter in the G(0) phase, HDAC3 is bound in early S phase. Activating function of HDAC3 towards the skp2 gene has been validated using RNA interference techniques. siRNAs, targeting HDAC3 specifically, reduced skp2 transcription.
These findings propose that the skp2 gene is a novel target of HDAC3, mediating cell cycle control and oncogenesis.
在各种模型中，组蛋白去乙酰化酶（HDACs）已与细胞周期调控相关联，涉及细胞周期蛋白依赖性激酶抑制剂p27（Kip1）的调节。
在此，我们证明曲古抑菌素A对HDAC的抑制作用可降低S期激酶相关蛋白2的mRNA和蛋白丰度。此外，与在G（0）期募集到skp2启动子的HDAC1不同，HDAC3在S期早期结合。利用RNA干扰技术已证实HDAC3对skp2基因具有激活功能。特异性靶向HDAC3的小干扰RNA（siRNAs）降低了skp2的转录。
这些发现表明skp2基因是HDAC3的一个新靶点，介导细胞周期调控和肿瘤发生。
