Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Allosteric Regulation01:08

Allosteric Regulation

Allosteric regulation of enzymes occurs when the binding of an effector molecule to a site that is different from the active site causes a change in the enzymatic activity. This alternate site is called an allosteric site, and an enzyme can contain more than one of these sites. Allosteric regulation can either be positive or negative, resulting in an increase or decrease in enzyme activity. Most enzymes that display allosteric regulation are metabolic enzymes involved in the degradation or...
Allosteric Regulation01:08

Allosteric Regulation

Allosteric regulation of enzymes occurs when the binding of an effector molecule to a site that is different from the active site causes a change in the enzymatic activity. This alternate site is called an allosteric site, and an enzyme can contain more than one of these sites. Allosteric regulation can either be positive or negative, resulting in an increase or decrease in enzyme activity. Most enzymes that display allosteric regulation are metabolic enzymes involved in the degradation or...
The Proteasome01:13

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 (ubiquitin...
The Proteasome02:18

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 Proteasome02:18

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...
Allosteric Proteins-ATCase01:19

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 pathway,...

You might also read

Related Articles

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

Sort by
Same author

Tetra-anionic porphyrin mimics protein-protein interactions between regulatory particles and the catalytic core, allosterically activating human 20S proteasome.

Journal of enzyme inhibition and medicinal chemistry·2025
Same author

Androgen deprivation-induced elevated nuclear SIRT1 promotes prostate tumor cell survival by reactivation of AR signaling.

Cancer letters·2021
Same author

Long-term effects of direct current are reproduced by intermittent depolarization of myelinated nerve fibers.

Journal of neurophysiology·2018
Same author

Thin film absorption characterization by focus error thermal lensing.

The Review of scientific instruments·2018
Same author

Analysis of surface deformation in thin-film coatings by carrier frequency interferometry.

Applied optics·2017
Same author

Does trans-spinal and local DC polarization affect presynaptic inhibition and post-activation depression?

The Journal of physiology·2016

Related Experiment Video

Updated: Jun 16, 2026

Monitoring of Ubiquitin-proteasome Activity in Living Cells Using a Degron (dgn)-destabilized Green Fluorescent Protein (GFP)-based Reporter Protein
10:25

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

Potential allosteric modulators of the proteasome activity.

E Jankowska1, M Gaczynska, P Osmulski

  • 1Faculty of Chemistry, University of Gdansk, Sobieskiego 18, Gdansk 80-952, Poland. elaj@chem.univ.gda.pl

Biopolymers
|January 22, 2010
PubMed
Summary

Researchers explored novel noncompetitive proteasome inhibitors using peptides derived from HIV-1 Tat and PA28. Tat peptides inhibited the proteasome, while Tat2 activated it at low concentrations, offering precise therapeutic regulation strategies.

More Related Videos

Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates
09:47

Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates

Published on: May 10, 2022

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
10:44

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

Published on: May 15, 2019

Related Experiment Videos

Last Updated: Jun 16, 2026

Monitoring of Ubiquitin-proteasome Activity in Living Cells Using a Degron (dgn)-destabilized Green Fluorescent Protein (GFP)-based Reporter Protein
10:25

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

Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates
09:47

Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates

Published on: May 10, 2022

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
10:44

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

Published on: May 15, 2019

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Drug Discovery

Background:

  • The proteasome is crucial for cellular regulation and a target for cancer, inflammatory, and degenerative diseases.
  • Current drug development focuses on competitive proteasome inhibitors.
  • Noncompetitive inhibitors offer a potential strategy for precise proteasome regulation.

Purpose of the Study:

  • To evaluate short peptides derived from HIV-1 Tat and PA28 as potential noncompetitive proteasome modulators.
  • To investigate the peptides' effects on proteasome core particle activity and regulatory module function.

Main Methods:

  • Circular Dichroism (CD)
  • Fourier Transformed Infrared Spectroscopy (FTIR)
  • Nuclear Magnetic Resonance (NMR) analysis
  • Molecular Dynamics (MD) simulations

Main Results:

  • Tat peptides containing PP2 acted as noncompetitive proteasome inhibitors, disrupting PA28alphabeta activator function.
  • Tat2 peptide demonstrated proteasome activation at low concentrations.
  • PA28-derived peptides showed minimal direct effects but cooperated with PA28alphabeta activity.

Conclusions:

  • Short peptides, particularly Tat-derived ones, can act as noncompetitive proteasome inhibitors or activators.
  • These findings support the development of small molecules for precise proteasome activity modulation.
  • Peptide-based strategies offer a promising avenue for therapeutic intervention in diseases involving proteasome dysfunction.