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Title: Downregulation of Ras C-terminal processing by JNK inhibition. Author: Mouri W, Tachibana K, Tomiyama A, Sunayama J, Sato A, Sakurada K, Kayama T, Kitanaka C. Journal: Biochem Biophys Res Commun; 2008 Jun 27; 371(2):273-7. PubMed ID: 18435909. Abstract: 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.[Abstract] [Full Text] [Related] [New Search]