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Mini-Reviews in Medicinal Chemistry

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ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

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Ras Dimer Formation as a New Signaling Mechanism and Potential Cancer Therapeutic Target

Author(s): Mo Chen, Alec Peters, Tao Huang and Xiaolin Nan

Volume 16, Issue 5, 2016

Page: [391 - 403] Pages: 13

DOI: 10.2174/1389557515666151001152212

open access plus

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.

Keywords: Ras signaling, Ras dimer, membrane clustering, cancer, targeted therapy.

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