Article thumbnail

Chemical Biology Tools for Regulating RAS Signaling Complexity in Space and Time

By Hilde van Hattum and Herbert Waldmann

Abstract

Rat sarcoma (RAS) family members are small GTPases that control a number of signaling pathways important for normal cellular proliferation. Therefore, it is no surprise that a significant portion of human tumors express constitutively active mutated RAS proteins, which leads to deregulation of RAS signaling pathways, resulting in pathological perturbations of cell growth and death. Although the molecular details of RAS signaling cascades are well understood, there is still a largely unmet need for small molecule probes to control RAS signaling in space and time. More broadly, given the prevalence of mutated RAS in cancer, the need to translate the insights obtained from using small molecule probes into clinically useful drugs is also significant. In this review, we introduce RAS proteins and the signaling pathways they are involved in, and discuss some of the innovative chemical biology approaches to regulate RAS signaling, which include the exploitation of newly identified binding pockets, covalent inhibitors for mutated RAS, and RAS localization impairment

Publisher: Elsevier Ltd.
Year: 2014
DOI identifier: 10.1016/j.chembiol.2014.08.001
OAI identifier:

Suggested articles


To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.