Downregulation of Ras C-terminal processing by JNK inhibition
| Autor: | Kaori Sakurada, Arata Tomiyama, Ken Tachibana, Wataru Mouri, Jun Sunayama, Chifumi Kitanaka, Takamasa Kayama, Atsushi Sato |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Regulation of gene expression
Cell type Cell growth MAP Kinase Kinase 4 Ultraviolet Rays Biophysics Down-Regulation Translation (biology) Cell Count Cell Biology Biology Oncogene Protein p21(ras) Biochemistry Cell biology Proto-Oncogene Proteins p21(ras) Downregulation and upregulation Anti-apoptotic Ras signalling cascade Cell Line Tumor Ultraviolet irradiation Humans Autocrine signalling Molecular Biology Protein Processing Post-Translational Signal Transduction |
| Zdroj: | Biochemical and biophysical research communications. 371(2) |
| ISSN: | 1090-2104 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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