The study of cell-cycle dependent degradation of the Notch intracellular domain

Notch信号通路在重要的细胞命运决定中起着至关重要的作用。Notch信号的激活是由Notch受体和Delta样配体之间的胞外相互作用触发的，并通过蛋白降解过程导致Notch胞内域(NICD)的释放。NiCd进入细胞核，通过与多种因子形成复合体，发挥转录因子的作用。NiCd是一种不稳定的蛋白质，其降解由SCF E3泛素连接酶介导，在调控Notch信号转导中起着重要作用。在这项研究中，我们发现NICD在细胞周期中从后期降解到G1期，这种细胞周期依赖性的降解是由SCF-Skp2 E3泛素连接酶介导的。此外，我们还发现，只有F-box蛋白与NICD-Skp2复合体相互作用，调节NICD的细胞周期依赖性降解。这些结果提出了Notch信号通路可能以细胞周期依赖的方式进行调节的可能性。

The Notch signaling pathway plays crucial roles in important cell fate decisions. Activation of Notch signaling is triggered by extracellular interactions between Notch receptors and Delta-like ligands, and results in the release of the Notch intracellular domain (NICD) by proteolytic processing. NICD enters the nucleus, and acts as a transcriptional factor by forming a complex with several factors. NICD is an unstable protein and its degradation mediated by the SCF E3 ubiquitin ligase plays an important role in regulating the Notch signaling. In this study, we show that NICD is degraded from anaphase to G1 phase in the cell cycle, and that this cell-cycle dependent degradation is mediated by the SCF-Skp2 E3 ubiquitin ligase. In addition, we found that an F-box only protein interacts with NICD-Skp2 complex to regulate the cell-cycle dependent degradation of NICD. These results raise the possibility that the Notch signaling pathway might be regulated in cell-cycle dependent manner.