Mouri Wataru, Tachibana Ken, Tomiyama Arata, Sunayama Jun, Sato Atsushi, Sakurada Kaori, Kayama Takamasa, Kitanaka Chifumi
Department of Molecular Cancer Science, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan.
Biochem Biophys Res Commun. 2008 Jun 27;371(2):273-7. doi: 10.1016/j.bbrc.2008.04.057. Epub 2008 Apr 22.
After translation, Ras proteins undergo a series of modifications at their C-termini. This post-translational C-terminal processing is essential for Ras to become functional, but it remains unknown whether and how Ras C-terminal processing is regulated. Here we show that the C-terminal processing and subsequent plasma membrane localization of H-Ras as well as the activation of the downstream signaling pathways by H-Ras are prevented by JNK inhibition. Conversely, JNK activation by ultraviolet irradiation resulted in promotion of C-terminal processing of H-Ras. Furthermore, increased cell density promoted C-terminal processing of H-Ras most likely through an autocrine/paracrine mechanism, which was also blocked under JNK-inhibited condition. Ras C-terminal processing was sensitive to JNK inhibition in the case of H- and N-Ras but not K-Ras, and in a variety of cell types. Thus, our results suggest for the first time that Ras C-terminal processing is a regulated mechanism in which JNK is involved.
翻译后，Ras蛋白在其C末端会经历一系列修饰。这种翻译后C末端加工对于Ras发挥功能至关重要，但Ras C末端加工是否以及如何受到调控仍不清楚。在这里，我们表明，JNK抑制可阻止H-Ras的C末端加工以及随后的质膜定位，以及H-Ras对下游信号通路的激活。相反，紫外线照射激活JNK会促进H-Ras的C末端加工。此外，细胞密度增加最有可能通过自分泌/旁分泌机制促进H-Ras的C末端加工，而在JNK抑制条件下这种促进作用也会被阻断。在H-Ras和N-Ras的情况下，Ras C末端加工对JNK抑制敏感，但K-Ras则不敏感，并且在多种细胞类型中均如此。因此，我们的结果首次表明，Ras C末端加工是一种受调控的机制，其中JNK参与其中。
