title: Downregulation of Ras C-terminal processing by JNK inhibition.
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.
authors.affiliation: Department of Molecular Cancer Science, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Mouri
authors.forename: Ken
authors.initials: K
authors.lastname: Tachibana
authors.forename: Arata
authors.initials: A
authors.lastname: Tomiyama
authors.forename: Jun
authors.initials: J
authors.lastname: Sunayama
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sato
authors.forename: Kaori
authors.initials: K
authors.lastname: Sakurada
authors.forename: Takamasa
authors.initials: T
authors.lastname: Kayama
authors.forename: Chifumi
authors.initials: C
authors.lastname: Kitanaka
mesh_terms: D002452:Cell Count; D045744:Cell Line, Tumor; D015536:Down-Regulation; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000528:radiation effects; D015689:Oncogene Protein p21(ras) / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D016283:Proto-Oncogene Proteins p21(ras) / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014466:Ultraviolet Rays
chemical_list: D048670:MAP Kinase Kinase 4; D015689:Oncogene Protein p21(ras); D016283:Proto-Oncogene Proteins p21(ras)