Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Related Concept Videos

The Proteasome

The Proteasome

Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...

The Proteasome

The Proteasome

Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...

The Proteasome

The Proteasome

The Proteasome Structure

The Proteasome Structure

The ubiquitin-proteasome pathway is a well-known mechanism utilized by eukaryotic cells to remove cytoplasmic proteins that are misfolded, damaged, or no longer needed. In this pathway, the protein that needs to be eliminated undergoes a process called ubiquitination, where a chain of ubiquitin molecules is attached to the 48th lysine residue of the target protein. This ubiquitin modification helps the proteasome distinguish between a target protein and a healthy protein.
The proteasome is an...

Anticholinesterase Agents: Poisoning and Treatment

Anticholinesterase Agents: Poisoning and Treatment

Anticholinesterases, also known as cholinesterase inhibitors, work by blocking the breakdown of acetylcholine, leading to its accumulation in the synaptic cleft. This accumulation indirectly enhances both muscarinic and nicotinic actions. These agents are classified as reversible or irreversible based on their mechanism of action.
Irreversible agents form a strong bond with the cholinesterase enzyme, making it inactive. The breakdown of the phosphorylated enzyme is...

Allosteric Proteins-ATCase

Allosteric Proteins-ATCase

Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by

Same author

SIRT2-mediated deacetylation activates USP22 catalytic function for PD-L1 protein stabilization and tumor immune escape.

The Journal of clinical investigation·2026

Same author

Multilayered microelectrode array for monitoring electrophysiological signals of 3d neural networks in cerebral organoid.

Microsystems & nanoengineering·2026

Same author

A novel S1P analogue/MLCK inhibitory peptide-encargoed nanocarrier to attenuate lung vascular leak.

American journal of respiratory cell and molecular biology·2026

Same author

Natural Products Inspired Scaffold Diversification Leads to Unnatural Molecular Warhead and Covalent Strategy to Modulating Protein Function through Electrophilic Bromine Transfer.

Advanced science (Weinheim, Baden-Wurttemberg, Germany)·2026

Same author

GRP78 Selective Inhibitors From a Direct-to-Biology Strategy.

Angewandte Chemie (International ed. in English)·2026

Same author

Involvement of Non-Muscle Myosin Light Chain Kinase Nitration in Molecular Regulation of Inflammation-Induced Endothelial Cell Barrier Dysfunction.

Cells·2026

Search research articles

Related Experiment Video

Updated: Feb 28, 2026

Monitoring of Ubiquitin-proteasome Activity in Living Cells Using a Degron dgn-destabilized Green Fluorescent Protein GFP-based Reporter Protein

Monitoring of Ubiquitin-proteasome Activity in Living Cells Using a Degron dgn-destabilized Green Fluorescent Protein GFP-based Reporter Protein

Published on: November 10, 2012

Arsenic Compromises Both p97 and Proteasome Functions.

Joseph Tillotson¹, Christopher J Zerio¹, Bryan Harder¹

¹Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona , 1703 East Mabel Street, P.O. Box 210207, Tucson, Arizona 85721, United States.

Chemical Research in Toxicology

|June 22, 2017

Summary

Arsenic exposure disrupts cellular protein quality control by impairing the p97 chaperone and proteasome systems. This dysfunction explains severe issues seen in acute arsenic poisoning.

More Related Videos

Examining Proteasome Assembly with Recombinant Archaeal Proteasomes and Nondenaturing PAGE: The Case for a Combined Approach

Examining Proteasome Assembly with Recombinant Archaeal Proteasomes and Nondenaturing PAGE: The Case for a Combined Approach

Published on: December 17, 2016

In-vitro Reconstitution of Bacterial Ubiquitination and VCP/p97-mediated Elimination

In-vitro Reconstitution of Bacterial Ubiquitination and VCP/p97-mediated Elimination

Published on: January 2, 2026

Related Experiment Videos

Last Updated: Feb 28, 2026

Monitoring of Ubiquitin-proteasome Activity in Living Cells Using a Degron dgn-destabilized Green Fluorescent Protein GFP-based Reporter Protein

Monitoring of Ubiquitin-proteasome Activity in Living Cells Using a Degron dgn-destabilized Green Fluorescent Protein GFP-based Reporter Protein

Published on: November 10, 2012

Examining Proteasome Assembly with Recombinant Archaeal Proteasomes and Nondenaturing PAGE: The Case for a Combined Approach

Examining Proteasome Assembly with Recombinant Archaeal Proteasomes and Nondenaturing PAGE: The Case for a Combined Approach

Published on: December 17, 2016

In-vitro Reconstitution of Bacterial Ubiquitination and VCP/p97-mediated Elimination

In-vitro Reconstitution of Bacterial Ubiquitination and VCP/p97-mediated Elimination

Published on: January 2, 2026

Area of Science:

Environmental Toxicology
Molecular Biology
Cellular Biology

Background:

Arsenic toxicity affects over 200 million globally, with mechanisms obscured by its diverse effects.
Previous research links arsenic to compromised protein quality control via the ubiquitin proteasome system (UPS) and ER-associated degradation (ERAD).

Purpose of the Study:

To investigate the direct link between arsenic exposure and protein quality control mechanisms.
To elucidate the specific molecular pathways affected by arsenic in cellular protein homeostasis.

Main Methods:

Utilized biochemical and cellular assays to examine the function of the p97 ATPase.
Employed a well-characterized reporter system to assess proteasome and p97 function in arsenic-exposed cells.

Main Results:

Demonstrated arsenic-induced misregulation of the p97 ATPase associated with various cellular activities (AAA+) chaperone's ATPase cycle.
Observed an increased rate of ATP hydrolysis in p97, mimicking pathogenic mutations.
Confirmed compromised proteasome function alongside p97 dysfunction in cellular studies.

Conclusions:

Arsenic exposure disrupts protein quality control by impairing both p97 and proteasome functions.
The combined loss of p97 and proteasome activity provides a mechanistic explanation for severe protein quality control issues in acute arsenic poisoning.