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Nat Rev Mol Cell Biol. 2011 Dec 22;13(1):39-51. doi: 10.1038/nrm3255.

Regulating the regulator: post-translational modification of RAS.

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1
NYU School of Medicine, 550 First Avenue, New York, NY 10016, USA.

Abstract

RAS proteins are monomeric GTPases that act as binary molecular switches to regulate a wide range of cellular processes. The exchange of GTP for GDP on RAS is regulated by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), which regulate the activation state of RAS without covalently modifying it. By contrast, post-translational modifications (PTMs) of RAS proteins direct them to various cellular membranes and, in some cases, modulate GTP-GDP exchange. Important RAS PTMs include the constitutive and irreversible remodelling of its carboxy-terminal CAAX motif by farnesylation, proteolysis and methylation, reversible palmitoylation, and conditional modifications, including phosphorylation, peptidyl-prolyl isomerisation, monoubiquitylation, diubiquitylation, nitrosylation, ADP ribosylation and glucosylation.

PMID:
22189424
PMCID:
PMC3879958
DOI:
10.1038/nrm3255
[Indexed for MEDLINE]
Free PMC Article
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