Abstract
There 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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Brefeldin A / therapeutic use
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Drug Discovery
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GTPase-Activating Proteins / antagonists & inhibitors*
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GTPase-Activating Proteins / physiology
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Guanine Nucleotide Exchange Factors / antagonists & inhibitors*
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Guanine Nucleotide Exchange Factors / physiology
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Humans
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Neoplasms / drug therapy*
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Neoplasms / etiology
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Neoplasms / metabolism
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Proto-Oncogene Proteins / physiology
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T-Lymphoma Invasion and Metastasis-inducing Protein 1
Substances
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ECT2 protein, human
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GTPase-Activating Proteins
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Guanine Nucleotide Exchange Factors
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PREX1 protein, human
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Proto-Oncogene Proteins
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T-Lymphoma Invasion and Metastasis-inducing Protein 1
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TIAM1 protein, human
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Brefeldin A