Radicicol leads to selective depletion of Raf kinase and disrupts K-Ras-activated aberrant signaling pathway.

The Journal of Biological Chemistry
S SogaM Hara

Abstract

Activation of Ras leads to the constitutive activation of a downstream phosphorylation cascade comprised of Raf-1, mitogen-activated protein kinase (MAPK) kinase, and MAPK. We have developed a yeast-based assay in which the Saccharomyces cerevisiae mating pheromone-induced MAPK pathway relied on co-expression of K-Ras and Raf-1. Radicicol, an antifungal antibiotic, was found to inhibit the K-ras signaling pathway reconstituted in yeast. In K-ras-transformed, rat epithelial, and K-ras-activated, human pancreatic carcinoma cell lines, radicicol inhibited K-Ras-induced hyperphosphorylation of Erk2. In addition, the level of Raf kinase was significantly decreased in radicicol-treated cells, whereas the levels of K-Ras and MAPK remained unchanged. These results suggest that radicicol disrupts the K-Ras-activated signaling pathway by selectively depleting Raf kinase and raises the possibility that pharmacological destabilization of Raf kinase could be a new and powerful approach for the treatment of K-ras-activated human cancers.

References

Mar 1, 1992·Bioscience, Biotechnology, and Biochemistry·H J KwonT Beppu
Sep 10, 1992·Nature·J SettlemanR A Weinberg
Oct 15, 1985·Biochemical and Biophysical Research Communications·T TamaokiH Nakano
Jan 1, 1983·Journal of Bacteriology·H ItoA Kimura
Nov 1, 1995·Molecular and Cellular Biology·R Khosravi-FarC J Der
Sep 14, 1993·European Journal of Pharmacology·T OikawaS Murota
Mar 30, 1995·Nature·R G QiuM Symons
Mar 30, 1994·Biochemical and Biophysical Research Communications·T J HallM Missbach
Apr 1, 1993·Current Opinion in Cell Biology·B Errede, D E Levin
Dec 24, 1996·Proceedings of the National Academy of Sciences of the United States of America·B P MoniaD Fabbro
Feb 21, 1953·Nature·P DELMOTTE, J DELMOTTE-PLAQUE

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Feb 19, 2000·Current Opinion in Structural Biology·L H Pearl, C Prodromou
Sep 6, 2002·Bioorganic & Medicinal Chemistry·Tsutomu AgatsumaYutaka Saitoh
Oct 20, 2005·Journal of Bioscience and Bioengineering·K FujitaM Taniguchi
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Nov 27, 2009·Journal of Virology·Laura RiolobosJosé M Almendral
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Aug 16, 2013·The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology·Cha Kyung YounYoung Jin Jeon
Jun 15, 2005·Angewandte Chemie·Hang Yin, Andrew D Hamilton
Jun 30, 2001·Canadian Journal of Physiology and Pharmacology·J J McGuireC R Triggle
Mar 19, 2016·Biopolymers·Laurence H Pearl
Feb 1, 2000·The Journal of Biological Chemistry·S J FeltsD O Toft
Jan 11, 2013·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Shiro Soga
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Oct 21, 2016·The Journal of Biological Chemistry·Shahana MitraAtin K Mandal
Sep 29, 2000·The Journal of Biological Chemistry·S W KiS Horinouchi
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