Regulation of by protein degradation and transport.

Sekiguchi研究了大分子复合体的核质转运机制，主要研究了GTP结合蛋白RAN相关蛋白RCC1、RRAG A/GTR1、DDX3。RCC1是一种染色质结合蛋白和一种鸟嘌呤交换因子。在本研究中，我们发现Gtrlp与Ran结合蛋白Yrb2p、核糖体生物发生蛋白Rpcl9p和Nop8p相互作用。我们还发现RRAG A与GTP结合蛋白RRAG C和RRAG D以及一种新的核仁蛋白NOP132相互作用。我们分离到了在核糖体生物发生和翻译中起作用的RNA死盒解旋酶DDX3的温度敏感突变体。结果表明，DDX3在仓鼠细胞周期蛋白A的表达中起作用。Nakayama研究了哺乳动物Skp2和Fbw7，这是一种SCF型泛素连接酶的F-box蛋白成分。Fbw7针对c-Myc、Notch、c-jun和Cyclin E，所有这些都能促进细胞周期，以实现泛素依赖的蛋白分解。临床证据表明，Fbw7功能丧失会导致…更多的癌症发展。我们产生了缺乏Fbw7的小鼠，发现胚胎在子宫中死亡，在血管发育方面表现出显著的异常。为了研究Fbw7在细胞分化过程中细胞周期控制中的作用，我们培育了Fbw7仅在T细胞系中被去除的小鼠(Fbw7条件基因敲除小鼠：CKO)。我们使用了两个启动子来表达Cre转基因株，LCK-启动子和CD4-启动子。在这两个病例中，Fbw7 CKO均可见胸腺增生，并伴有CD4+CD8+细胞的特异性扩增。在正常小鼠中，T细胞主要在CD4-CD8阶段增殖，细胞周期在CD4+CD8+阶段停止，而Fbw7 CKO小鼠在CD4+CD8+阶段细胞周期仍处于激活状态。在CD4+CD8+期，CKO、c-Myc和Notch高度积聚，而Cyclin E水平未受影响。Fbw7 CKO小鼠易患淋巴瘤。这些数据表明，Fbw7对于细胞周期在CD4+CD8+期的停滞是不可或缺的，而Fbw7的缺失会导致淋巴瘤的发生。较少

Sekiguchi has studied mechanisms of nuclear-cytoplasmic transport of macromolecuar complex, mainly on GTP binding protein Ran related proteins, RCC1, RRAG A/GTR1, DDX3. RCC1 is a chromatin binding protein and a Ran Guanine exchange factor. In this study, we found that Gtrlp interacts to Ran-binding protein, Yrb2p, ribosome biogenesis proteins, Rpcl9p and Nop8p. We also found that RRAG A interacts to GTP binding proteins, RRAG C and RRAG D, and a novel nucleolar protein, NOP132. We isolated hamster temperature-sensitive mutant of DDX3, an RNA DEAD-box helicase playing roles in ribosome biogenesis and translation. DDX3 turned out to play a role in cyclin A expression in hamster cells. Nakayama investigates mammalian Skp2 and Fbw7, which are F-box protein components of an SCF-type ubiquitin ligase. Fbw7 targets c-Myc, Notch, c-Jun, and cyclin E, all of which function to promote cell cycle, for ubiquitin-dependent proteolysis. Clinical evidence suggests that loss of Fbw7 function results i … More n cancer development. We generated mice deficient in Fbw7 and found that the embryos died in utero, manifesting marked abnormalities in vascular development. To investigate the role of Fbw7 in cell-cycle control during cellular differentiation, we have generated mice in which Fbw7 is ablated only in T-cell lineage (Fbw7 conditional knockout mice: CKO). We used two promoters for Cre-expressing transgenic lines, Lck-promoter and CD4-promoter. In both cases, thymic hyperplasia was observed in Fbw7 CKO with specific expansion of CD4+CD8+ population. In normal mice, T cells are mainly proliferated at CD4-CD8-stage, and cell cycle ceases at CD4+CD8+ stage, whereas cell cycle remained activated at CD4+CD8+ stage in Fbw7 CKO. In CD4+CD8+ stage of Fbw7 CKO, c-Myc and Notch highly accumulated, whereas cyclin E levels were unaffected. Fbw7 CKO mice are predisposed to lymphomas. These data suggest that Fbw7 is indispensable for the cell cycle arrest at CD4+CD8+ stage, and loss of Fbw7 results in lymphomatogenesis. Less