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Ras superfamily GEFs and GAPs: validated and tractable targets for cancer therapy?Vigil D; Cherfils J; Rossman KL; Der CJNat Rev Cancer 2010[Dec]; 10 (12): 842-57There is now considerable and increasing evidence for a causal role for aberrant activity of the Ras superfamily of small GTPases in human cancers. These GTPases function as GDP-GTP-regulated binary switches that control many fundamental cellular processes. A common mechanism of GTPase deregulation in cancer is the deregulated expression and/or activity of their regulatory proteins, guanine nucleotide exchange factors (GEFs) that promote formation of the active GTP-bound state and GTPase-activating proteins (GAPs) that return the GTPase to its GDP-bound inactive state. In this Review, we assess the association of GEFs and GAPs with cancer and their druggability for cancer therapeutics.|Animals[MESH]|Brefeldin A/therapeutic use[MESH]|Drug Discovery[MESH]|GTPase-Activating Proteins/*antagonists & inhibitors/physiology[MESH]|Guanine Nucleotide Exchange Factors/*antagonists & inhibitors/physiology[MESH]|Humans[MESH]|Neoplasms/*drug therapy/etiology/metabolism[MESH]|Proto-Oncogene Proteins/physiology[MESH]|T-Lymphoma Invasion and Metastasis-inducing Protein 1[MESH] |
