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Updated: Sep 28, 2025

Detection of Small GTPase Prenylation and GTP Binding Using Membrane Fractionation and GTPase-linked Immunosorbent Assay
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Detection of Small GTPase Prenylation and GTP Binding Using Membrane Fractionation and GTPase-linked Immunosorbent Assay

Published on: November 11, 2018

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Functional diversity in the RAS subfamily of small GTPases

Gabriela Bernal Astrain1, Maya Nikolova1, Matthew J Smith1,2

  • 1Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec H3T 1J4, Canada.

Biochemical Society Transactions
|March 31, 2022
PubMed

Insights

This study explores understudied RAS GTPases, revealing 17 may act as tumor suppressors, not oncogenes. These proteins, frequently downregulated in cancer, offer new therapeutic targets for cancer progression.

Area of Science:

  • Molecular Biology
  • Oncology
  • Cellular Signaling

Background:

  • RAS small GTPases are key regulators of cellular signaling pathways and are implicated in cancer development.
  • Research has primarily focused on oncogenic RAS genes (HRAS, KRAS, NRAS), neglecting other subfamily members.
  • The RAS subfamily comprises 35 GTPases with diverse functions, many of which remain understudied.

Purpose of the Study:

  • To investigate the role of understudied RAS GTPases in cancer.
  • To identify RAS GTPases that may function as tumor suppressors.
  • To characterize two novel families of RAS GTPases: distal-RAS (D-RAS) and CaaX-Less RAS (CL-RAS).

Main Methods:

  • Bioinformatic analysis of RAS GTPase expression in cancer datasets.
  • Literature review of existing evidence on understudied RAS GTPases.
  • Classification of identified RAS GTPases into functional families.

Main Results:

  • Identified 17 poorly characterized RAS GTPases frequently downregulated in cancer.
  • Evidence suggests these GTPases function as tumor suppressors, contrasting with known oncogenic RAS.
  • These GTPases cluster into two families: D-RAS (DIRAS, RASD, RASL10) and CL-RAS (RGK, NKIRAS, RERG, RASL11/12).

Conclusions:

  • Understudied RAS GTPases, particularly those in the D-RAS and CL-RAS families, show potential as tumor suppressors.
  • The RAS subfamily may collectively regulate cellular proliferation, with both oncogenic and tumor-suppressive members.
  • Further research into these enigmatic GTPases is warranted for understanding cancer biology and developing novel therapies.
Keywords:
G-proteinsGTPaseRAScell proliferationoncogenesistumour suppressors

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