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Updated: Apr 26, 2026

Fully Processed Recombinant KRAS4b: Isolating and Characterizing the Farnesylated and Methylated Protein
Published on: January 16, 2020
Posttranslational modifications of RAS: few pockets but many bumps
Mercedes Fissore-O'Leary1, Mark Philips1
1Perlmutter Cancer Center, 12296 NYU Grossman School of Medicine , 550 First Avenue, New York, NY 10016, USA.
Abstract:
RAS proteins control signals required for cell growth and survival and, when constitutively activated by mutation, can drive oncogenesis. RAS proteins are primarily regulated by their GTP or GDP binding state, which is controlled by guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs). RAS proteins are also substrates for dozens of posttranslational modifications (PTMs) that target them to membranes and serve as a secondary means of regulation. Because the newly developed direct RAS inhibitors do not produce durable responses in RAS-dependent cancer, there is renewed interest in targeting the PTMs of RAS. These modifications are the subject of this review.
Insights
RAS proteins regulate cell growth and survival. Targeting their posttranslational modifications (PTMs) offers a new strategy for treating RAS-dependent cancers when direct inhibitors fail.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- RAS proteins are key regulators of cellular signaling pathways controlling growth and survival.
- Mutated RAS proteins can become constitutively active, driving oncogenesis.
- RAS activity is modulated by GTP/GDP binding, regulated by GEFs and GAPs, and by posttranslational modifications (PTMs).
Purpose of the Study:
- To review the role of posttranslational modifications (PTMs) in RAS protein regulation.
- To explore targeting RAS PTMs as a therapeutic strategy for RAS-dependent cancers.
Main Methods:
- Literature review of studies on RAS protein regulation and PTMs.
- Analysis of the impact of PTMs on RAS localization and function.
- Evaluation of therapeutic potential of targeting RAS PTMs.
Main Results:
- RAS proteins undergo numerous PTMs that influence their membrane localization and function.
- PTMs provide a secondary layer of regulation for RAS signaling.
- Direct RAS inhibitors have limitations in producing durable responses in cancer patients.
Conclusions:
- Targeting RAS PTMs represents a promising alternative therapeutic approach for RAS-driven cancers.
- Further research into RAS PTMs is warranted to develop novel cancer treatments.
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