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Updated: Aug 14, 2026

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells
10:27

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells

Published on: March 9, 2012

Site-specific processing of Ras and Rap1 Switch I by a MARTX toxin effector domain

Irena Antic1, Marco Biancucci1, Yueming Zhu2

  • 1Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue, Ward 6-225, Chicago, Illinois 60611, USA.

Nature Communications
|June 9, 2015
PubMed

Insights

A bacterial toxin specifically cleaves Ras and Rap1 proteins, inhibiting cell proliferation. This newly identified Ras/Rap1-specific endopeptidase (RRSP) family shows potential for targeting cancer-associated Ras mutations.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Microbiology

Background:

  • Ras proteins regulate cell growth and proliferation.
  • RAS gene mutations are linked to human carcinogenesis.

Purpose of the Study:

  • To investigate the enzymatic activity of the MARTX toxin-effector domain DUF5(Vv) from Vibrio vulnificus.
  • To determine if DUF5(Vv) can cleave Ras and Rap1 proteins and assess its impact on cell proliferation.

Main Methods:

  • Biochemical assays to demonstrate DUF5(Vv) endopeptidase activity.
  • Mammalian cell culture to observe DUF5(Vv) processing of Ras and its effect on ERK1/2 signaling.
  • Analysis of DUF5(Vv) homologues and their cleavage activity on Ras isoforms and mutant KRas.

Main Results:

  • DUF5(Vv) acts as a site-specific endopeptidase, cleaving Ras and Rap1 within the Switch 1 region.
  • DUF5(Vv) inactivates ERK1/2 signaling, leading to inhibited cell proliferation.
  • DUF5(Vv) homologues share the ability to cleave Ras and Rap1.
  • DUF5(Vv) effectively cleaves all Ras isoforms and common cancer-associated KRas mutations.

Conclusions:

  • A novel family of Ras/Rap1-specific endopeptidases (RRSPs) has been identified.
  • RRSPs, exemplified by DUF5(Vv), can inactivate both wild-type and mutant Ras proteins.
  • This enzyme family holds potential for therapeutic strategies against malignancies driven by Ras signaling.

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