Ras dimer formation as a new signaling mechanism and potential cancer therapeutic target

Mo Chen, Alec Peters, Tao Huang, Xiaolin Nan

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

The K-, N-, and HRas small GTPases are key regulators of cell physiology and are frequently mutated in human cancers. Despite intensive research, previous efforts to target hyperactive Ras based on known mechanisms of Ras signaling have been met with little success. Several studies have provided compelling evidence for the existence and biological relevance of Ras dimers, establishing a new mechanism for regulating Ras activity in cells additionally to GTP-loading and membrane localization. Existing data also start to reveal how Ras proteins dimerize on the membrane. We propose a dimer model to describe Ras-mediated effector activation, which contrasts existing models of Ras signaling as a monomer or as a 5-8 membered multimer. We also discuss potential implications of this model in both basic and translational Ras biology.

Original languageEnglish (US)
Pages (from-to)391-403
Number of pages13
JournalMini-Reviews in Medicinal Chemistry
Volume16
Issue number5
DOIs
StatePublished - Mar 1 2016

Keywords

  • Cancer
  • Membrane clustering
  • Ras dimer
  • Ras signaling
  • Targeted therapy

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Cancer Research

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