Downregulation of Ras C-terminal processing by JNK inhibition |
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Authors: | Mouri Wataru Tachibana Ken Tomiyama Arata Sunayama Jun Sato Atsushi Sakurada Kaori Kayama Takamasa Kitanaka Chifumi |
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Institution: | a Department of Molecular Cancer Science, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan b Department of Neurosurgery, Yamagata University School of Medicine, Yamagata 990-9585, Japan c Biology Division, National Cancer Center Research Institute, Tokyo 104-0045, Japan |
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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. |
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Keywords: | Ras C-terminal processing JNK Regulation Post-translational modification |
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