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Updated: Jun 11, 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

Ras-related small GTPases RalA and RalB regulate cellular survival after ionizing radiation

Ambrose R Kidd1, Jared L Snider, Timothy D Martin

  • 1Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

International Journal of Radiation Oncology, Biology, Physics
|July 13, 2010
PubMed
Abstract

Insights

Both RalA and RalB GTPases promote cancer cell survival after ionizing radiation (IR). Suppressing RalA or RalB impairs DNA repair and IR resistance, suggesting novel therapeutic targets for radiation therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Radiation Biology

Background:

  • Oncogenic Ras activation confers resistance to ionizing radiation (IR) in cancer cells.
  • RalA and RalB are Ras-like GTPases crucial for tumor growth and survival.
  • The role of Ral GTPases in cellular response to IR remains largely uncharacterized.

Purpose of the Study:

  • To investigate the role of RalA and RalB in cellular responses to ionizing radiation (IR).
  • To determine if Ral GTPases contribute to K-Ras-dependent radioresistance in pancreatic cancer cells.

Main Methods:

  • Short hairpin RNA (shRNA) was used to stably knockdown K-Ras, RalA, RalB, RalBP1, and Sec5 in MIA PaCa-2 cells.
  • Clonogenic survival assays assessed reproductive cell survival post-IR.
  • GammaH2AX expression and PARP cleavage were measured to evaluate DNA double-strand breaks (DSBs) and apoptosis, respectively.

Main Results:

  • Knockdown of K-Ras, RalA, or RalB reduced colony-forming ability after IR.
  • Suppression of either RalA or RalB decreased the rate of DSB repair post-IR.
  • RalB knockdown, but not RalA, increased apoptosis, while neither RalBP1 nor Sec5 suppression affected colony formation.

Conclusions:

  • Both RalA and RalB contribute to K-Ras-dependent radioresistance in pancreatic cancer cells.
  • Ral-mediated radioresistance involves impaired DNA repair (RalA and RalB) and increased apoptosis susceptibility (RalB).
  • Ral-mediated radioresistance does not rely on RalBP1 or the exocyst complex, suggesting atypical or novel effectors are involved.

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