Related Experiment Video

Updated: Feb 21, 2026

Measurements of Physiological Stress Responses in C. Elegans
10:36

Measurements of Physiological Stress Responses in C. Elegans

Published on: May 21, 2020

15.1K

Epigenetic Control of NRF2-Directed Cellular Antioxidant Status in Dictating Life-Death Decisions

John D Hayes1, Albena T Dinkova-Kostova1

  • 1Jacqui Wood Cancer Centre, Division of Cancer Research, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, UK.

Molecular Cell
|October 7, 2017
PubMed

Insights

The tumor suppressor protein ARF triggers cancer cell death by blocking the master redox regulator NRF2. This study reveals ARF’s novel mechanism of inhibiting NRF2 acetylation and activation.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cellular Biology

Background:

  • The tumor suppressor protein ARF plays a critical role in cancer suppression.
  • NRF2 is a master regulator of the cellular redox balance, crucial for cell survival.
  • Posttranslational modifications, such as acetylation, are key to regulating protein function.

Purpose of the Study:

  • To elucidate the mechanism by which ARF sensitizes cancer cells to programmed cell death.
  • To investigate the interaction between ARF and the redox regulator NRF2.
  • To understand the role of ARF in the posttranslational regulation of NRF2.

Main Methods:

  • Co-immunoprecipitation assays to detect physical interaction between ARF and NRF2.
  • Western blotting to assess NRF2 acetylation levels.
  • Cell viability assays to measure programmed cell death in cancer cells.

Main Results:

  • Chen et al. demonstrate that ARF physically interacts with NRF2.
  • ARF antagonizes the acetylation and subsequent activation of NRF2.
  • This interaction leads to increased sensitization of cancer cells to programmed death.

Conclusions:

  • ARF acts as a tumor suppressor by inhibiting NRF2 activation through a novel mechanism of antagonizing its acetylation.
  • This provides an unusual mode of posttranslational NRF2 regulation and a potential therapeutic target in cancer.

More Related Videos

Protocol for the Differentiation of Human Induced Pluripotent Stem Cells into Mixed Cultures of Neurons and Glia for Neurotoxicity Testing09:02

Protocol for the Differentiation of Human Induced Pluripotent Stem Cells into Mixed Cultures of Neurons and Glia for Neurotoxicity Testing

Published on: June 9, 2017

24.5K
A Quantitative Measurement of Reactive Oxygen Species and Senescence-associated Secretory Phenotype in Normal Human Fibroblasts During Oncogene-induced Senescence13:59

A Quantitative Measurement of Reactive Oxygen Species and Senescence-associated Secretory Phenotype in Normal Human Fibroblasts During Oncogene-induced Senescence

Published on: August 12, 2018

8.6K

Related Concept Videos

Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
3.1K
Redox Reactions01:27

Redox Reactions

Redox reactions are vital biochemical processes that underpin energy metabolism in cells. These reactions involve the transfer of electrons between molecules, occurring in tandem as oxidation and reduction. Oxidation refers to the loss of electrons, while reduction denotes their gain. This coupling ensures the seamless flow of electrons through metabolic pathways. For example, in bacterial metabolism, glucose undergoes oxidation to carbon dioxide, while oxygen is simultaneously reduced to...
1.2K
Circadian Rhythms and Gene Regulation02:19

Circadian Rhythms and Gene Regulation

The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent...
4.6K
Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
19.2K
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.
38.6K
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
7.9K