Article
RAF inhibitors promote RAS-RAF interaction by allosterically disrupting RAF autoinhibition.
Nature communications - 31 Oct 2017
Jin Ting, Lavoie Hugo, Sahmi Malha, David Maud, Hilt Christine, Hammell Amy, Therrien Marc
Abstract excerpt
First-generation RAF inhibitors paradoxically induce ERK signaling in normal and tumor cells exhibiting RAS activity. Compound-induced RAF dimerization through stabilization of the RAF ON/active state by inhibitors has emerged as a critical contributing factor. RAF inhibitors also enhance RAS-RAF...
Topics
- Allosteric Regulation
- Cell Line, Tumor
- Extracellular Signal-Regulated MAP Kinases
- HEK293 Cells
- Humans
- Models, Biological
- Mutation
- Phosphorylation
- Protein Binding
- Protein Kinase Inhibitors
- Protein Multimerization
- Proto-Oncogene Proteins B-raf
- Proto-Oncogene Proteins c-raf
- Proto-Oncogene Proteins p21(ras)