Related Experiment Video

Updated: Apr 24, 2026

Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence
04:56

Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence

Published on: December 30, 2025

358

Ral GTPase down-regulation stabilizes and reactivates p53 to inhibit malignant transformation

Awet Tecleab1, Xiaolei Zhang2, Said M Sebti3

  • 1From the Drug Discovery Department, H. Lee Moffitt Cancer Center and Research Institute and the Departments of Oncologic Sciences and Molecular Medicine, University of South Florida, Tampa, Florida 33612.

The Journal of Biological Chemistry
|September 12, 2014
PubMed

Insights

Ras pathway proteins K-Ras and Ral GTPases (RalA, RalB) maintain low p53 levels in cancer. Their depletion stabilizes p53, suppressing malignant transformation and tumor growth.

Area of Science:

  • Molecular biology
  • Cancer research
  • Cell signaling

Background:

  • Ras GTPases are crucial for cell growth and cancer.
  • The precise role of Ral GTPases in malignant transformation is unclear.
  • Understanding K-Ras and Ral GTPase regulation of p53 is vital for cancer therapy.

Purpose of the Study:

  • Investigate the role of K-Ras and Ral GTPases in regulating p53 levels in cancer cells.
  • Determine the impact of K-Ras and Ral GTPase depletion on p53 stability and function.
  • Assess the effect of K-Ras and Ral GTPase down-regulation on cancer cell malignant behaviors.

Main Methods:

  • Analyzed expression of K-Ras, RalA, RalB, AKT1/2, and c-Raf in human cancer cells.
  • Utilized gene depletion techniques (e.g., siRNA) to reduce K-Ras, RalA, and RalB levels.
  • Measured p53 protein levels, p53 stability (via ATM kinase activation, phosphorylation, and half-life), and p21(WAF) expression.
  • Assessed anchorage-independent growth, invasion, and cell cycle progression.

Main Results:

  • K-Ras, RalB, and RalA expression is required to maintain low p53 levels in mutant K-Ras cancer cells.
  • Depletion of K-Ras, RalB, or RalA increases p53 protein levels and stability, enhancing p21(WAF) expression.
  • K-Ras and RalB depletion inhibits anchorage-independent growth and invasion, while RalA depletion inhibits invasion, all in a p53-dependent manner.
  • p53 stability was significantly increased (up to 6-fold) upon GTPase depletion.

Conclusions:

  • K-Ras and RalB, and possibly RalA, are critical for suppressing p53 activity in cancer.
  • Down-regulating these GTPases reactivates p53 by enhancing its stability, thereby suppressing malignant transformation.
  • Targeting K-Ras and Ral GTPases may offer a therapeutic strategy for reactivating p53 and inhibiting cancer progression.
Keywords:
ApoptosisCancer BiologyK-RasRalARalBRas ProteinSerine 15 PhosphorylationSignal Transductionp53

More Related Videos

Purification of Ubiquitinated p53 Proteins from Mammalian Cells10:55

Purification of Ubiquitinated p53 Proteins from Mammalian Cells

Published on: March 21, 2022

2.6K
Yeast As a Chassis for Developing Functional Assays to Study Human P5314:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

8.9K

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

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...
4.0K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
32.1K
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
2.3K
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
8.5K
GTPases and their Regulation02:14

GTPases and their Regulation

Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒  small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins,...
7.9K
GTPases and their Regulation02:14

GTPases and their Regulation

2.4K