Related Experiment Video

Updated: Feb 8, 2026

Purification of Ubiquitinated p53 Proteins from Mammalian Cells
10:55

Purification of Ubiquitinated p53 Proteins from Mammalian Cells

Published on: March 21, 2022

2.8K

Arsenic-induced apoptosis in the p53-proficient and p53-deficient cells through differential modulation of NFkB

Lei Yin1, Xiaozhong Yu2

  • 1Department of Environmental Health Science, College of Public Health, University of Georgia, 150 Green Street, Athens, GA 30602, USA. Fax: 706.542.7472; ReproTox Biotech LLC, 111 Riverbend Drive, Athens, Georgia, United States.

Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association
|June 27, 2018
PubMed

Insights

Arsenic exhibits dual effects as a carcinogen and chemotherapeutic agent. Its impact on the NF-kappaB pathway and cell death differs between p53+/+ and p53-/- cells, revealing distinct mechanisms.

Area of Science:

  • Toxicology
  • Molecular Biology
  • Cancer Research

Background:

  • Arsenic is recognized as both an environmental carcinogen and a chemotherapeutic agent.
  • The precise mechanisms underlying arsenic's dual role remain incompletely understood.
  • Investigating cellular responses to arsenic, particularly concerning the p53 tumor suppressor, is crucial.

Purpose of the Study:

  • To investigate the differential effects of arsenic on the NF-kappaB pathway and proinflammatory cytokines in mouse cells with and without p53.
  • To elucidate the molecular mechanisms contributing to arsenic's dual carcinogenic and chemotherapeutic properties.
  • To compare cell viability, apoptosis, and key signaling pathway activation in response to arsenic exposure.

Main Methods:

  • Utilized mouse p53+/+ and p53-/- cells for comparative analysis.
  • Assessed cell viability and apoptosis following arsenic treatment.
  • Analyzed the activation of SAPK/JNK, p38 MAPK, AKT, and NF-kappaB pathways.
  • Performed transcriptional regulatory network analysis to identify altered transcription factors.

Main Results:

  • Arsenic reduced cell viability and increased apoptosis in p53-/- cells compared to p53+/+ cells.
  • Activation of SAPK/JNK, p38 MAPK, and AKT pathways was observed, particularly in p53-/- cells.
  • Differential modulation of the NF-kappaB pathway was confirmed, with decreased p-NFκB p65 and p-IKKαβ in p53-/- cells and increases in p53+/+ cells.
  • Arsenic altered distinct sets of transcription factors depending on p53 status.

Conclusions:

  • Arsenic differentially modulates the NF-kappaB pathway in a p53-dependent manner.
  • The distinct mechanisms of cell death observed in p53+/+ and p53-/- cells may explain arsenic's dual role as a carcinogen and chemotherapeutic agent.
  • Understanding these differential responses is key to harnessing arsenic's therapeutic potential while mitigating its carcinogenic risks.
Keywords:
Apoptosis and transcription factorsArseniteGene expression profilingNFκBp53

More Related Videos

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

10.1K
Derivation of Thymic Lymphoma T-cell Lines from Atm-/- and p53-/- Mice17:59

Derivation of Thymic Lymphoma T-cell Lines from Atm-/- and p53-/- Mice

Published on: April 3, 2011

12.7K

Related Concept Videos

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
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size...
15.2K
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
9.7K
C4 Pathway and CAM01:27

C4 Pathway and CAM

Most plants use the C3 pathway for carbon fixation. However, some plants, such as sugar cane, corn, and cacti that grow in hot conditions, use alternative pathways to fix carbon and conserve energy loss due to photorespiration. Photorespiration is the process that occurs when the oxygen concentration is high. Under such conditions, the rubisco enzyme in the Calvin cycle binds O2 instead of CO2, which halts photosynthesis and consumes energy.
C4 Pathway
The C4 pathway is used by plants such as...
49.3K
Induced Pluripotent Stem Cells01:13

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different types of cells. Ordinarily, cells that have differentiated into a specific cell type are post-mitotic—that is, they no longer divide. However, scientists have found a way to reprogram these mature cells so that they “de-differentiate” and return to an unspecialized, proliferative state. These cells are also pluripotent like embryonic stem cells—able to produce all cell types—and are therefore...
28.1K
iPS Cell Differentiation01:22

iPS Cell Differentiation

The ability of induced pluripotent stem cells or iPSCs to differentiate into most body cell types has stimulated repair and regenerative medicine research over the past few decades. iPSC-derived blood cells, hepatocytes, beta islet cells, cardiomyocytes, neurons, and other cell types can repair injuries or regenerate damaged tissue in diseases such as diabetes and neurodegenerative disorders.
3.1K