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Regulation of Ras Signaling by S-Nitrosylation

Sónia Simão1,2, Rafaela Ribeiro Agostinho1,2, Antonio Martínez-Ruiz3,4

  • 1Algarve Biomedical Center Research Institute (ABC-RI), University of Algarve, 8005-139 Faro, Portugal.

Antioxidants (Basel, Switzerland)
|August 26, 2023
PubMed

Insights

Ras proteins, key in cell signaling and cancer, are regulated by S-nitrosylation. This post-translational modification impacts Ras membrane interactions, localization, and activity, particularly through nitric oxide (NO) action.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Ras proteins are crucial GTPases mediating signal transduction for cell proliferation, migration, differentiation, and survival.
  • Mutations in Ras genes are common in various cancers, highlighting their oncogenic potential.
  • Post-translational modifications (PTMs) dynamically regulate Ras protein function and intracellular behavior.

Purpose of the Study:

  • To review the impact of S-nitrosylation on Ras protein interactions with membranes.
  • To elucidate how S-nitrosylation affects Ras cellular localization and activity.
  • To understand the role of nitric oxide (NO) in modulating Ras signaling pathways.

Main Methods:

  • Literature review focusing on S-nitrosylation of Ras proteins.
  • Analysis of studies detailing Ras post-translational modifications.
  • Examination of the effects of NO on Ras protein dynamics and signaling.

Main Results:

  • S-nitrosylation, the attachment of a nitrosyl group from NO to cysteine residues, modifies Ras proteins.
  • The conserved Cys118 residue in Ras is a primary site for S-nitrosylation, influencing signal transduction.
  • S-nitrosylation affects Ras membrane association, cellular localization, and activity, impacting downstream pathways like MAPK and PI3K.

Conclusions:

  • Ras S-nitrosylation is a critical regulatory mechanism influencing Ras protein function and cellular signaling.
  • Understanding Ras S-nitrosylation provides insights into NO's role in cellular dynamics and disease.
  • Further research is needed to identify S-nitrosylation targets within the RalGEF pathway.
Keywords:
RasS-nitrosylationneuronal cellsnitric oxidepost-translational modifications

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