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Related Concept Videos

The Ras Gene02:38

The Ras Gene

5.7K
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
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Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

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Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
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MAPK Signaling Cascades01:07

MAPK Signaling Cascades

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Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
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The Ras Gene02:38

The Ras Gene

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Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

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Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
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Abnormal Proliferation02:23

Abnormal Proliferation

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Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
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The differential interactomes of the KRAS splice variants identify BIRC6 as a ubiquitin ligase for KRAS4A.

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Related Experiment Video

Updated: Apr 26, 2026

Fully Processed Recombinant KRAS4b: Isolating and Characterizing the Farnesylated and Methylated Protein
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Fully Processed Recombinant KRAS4b: Isolating and Characterizing the Farnesylated and Methylated Protein

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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.

Biological Chemistry
|April 24, 2026
PubMed
Summary

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.

Keywords:
RASpalmitoylationprenylationubiquitination

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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.