CDC6 与 ORC:origin 复合物结合

中文名称

通路描述

Cdc6 是酵母和人类细胞中 DNA 复制起始的调节因子 (Mendez and Stillman 2000)，但在两种系统中的作用机制不同。遗传学研究表明，Cdc6 蛋白的正常功能是限制 DNA 复制仅进行一次细胞周期。具体而言，Cdc6 可能作为 ATP 酶开关，与 Mcm2-7:Cdt1 结合于 Cdc6:ORC:origin 复合物之间发挥作用 (Lee and Bell 2000)。在 S. cerevisiae 中，Cdc6 蛋白在细胞周期的 M 期晚期表达，在 G1 期延长时也在 G1 期晚期表达。该蛋白半衰期较短，通过 SCF 复合物介导的泛素化蛋白酶体降解而被破坏 (Piatti et al. 1995, Drury et al. 1997, Drury et al. 2000, Perkins et al. 2001)。人类 Cdc6 蛋白水平在 G1 早期降低，但在细胞周期其余部分保持恒定 (Petersen et al. 2000)。一些报告指出，在细胞进入 S 期后，Cdc6 被磷酸化，被排除出细胞核，并受到泛素化和降解 (Saha et al. 1998, Jiang et al. 1999, Petersen et al. 1999)。G1 期补充 Cdc6 蛋白水平似乎由 E2F 转录因子调节 (Yan et al. 1998)。

英文描述

Negative regulation of MET activity Signaling by MET receptor is negatively regulated mainly by MET receptor dephosphorylation or MET receptor degradation. Protein tyrosine phosphatase PTPRJ dephosphorylates MET tyrosine residue Y1349, thus removing the docking site for the GAB1 adapter (Palka et al. 2003). Protein tyrosine phosphatases PTPN1 and PTPN2 dephosphorylate MET tyrosines Y1234 and Y1235 in the kinase activation loop, thus attenuating catalytic activity of MET (Sangwan et al. 2008). The E3 ubiquitin ligase CBL promotes ubiquitination of the activated MET receptor and subsequent MET degradation. CBL contains a RING finger domain that engages E2 protein ubiquitin ligases to mediate ubiquitination of MET, which may occur at the cell membrane or in the early endocytic compartment. Ubiquitinated MET is degraded in a late endosomal or lysosomal compartment in a proteasome-dependent manner. The involvement of proteasome in MET degradation seems to be indirect, through an effect on MET endocytic trafficking (Jeffers et al. 1997, Peschard et al. 2001, Hammond et al. 2001, Petrelli et al. 2002). LRIG1 promotes lysosome-dependent degradation of MET in the absence of HGF-mediated activation (Lee et al. 2014, Oh et al. 2014).
MET-mediated activation of RAS signaling is inhibited by MET receptor binding to MUC20 (Higuchi et al. 2004) or RANBP10 (Wang et al. 2004).

所含基因

20 个基因