Jove
Visualize
Contact Us

Related Concept Videos

Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

6.7K
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....
6.7K
Regulated Protein Degradation02:58

Regulated Protein Degradation

2.4K
2.4K

You might also read

Related Articles

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

Sort by
Same author

Intracellular delivery of full-length antibodies via organ-targeted lipid nanoparticles.

Proceedings of the National Academy of Sciences of the United States of America·2026
Same author

Utility of the Frontal-Plane QRS-T Angle in a Real-World Screening Population, for Identification of Hypertrophic Cardiomyopathy.

Pediatric cardiology·2026
Same author

AI-Designed Peptides as Tools for Biochemistry.

Biochemistry·2026
Same author

Predicting Firearm Suicide among US Army Veterans Transitioning from Active Service.

Nature. Mental health·2026
Same author

Joint models targeting U.S. Army soldiers at high-risk of post-separation unemployment, homelessness, and suicide-related behaviors.

Npj mental health research·2026
Same author

Topological reprogramming transforms an integral membrane oligosaccharyltransferase into a water-soluble glycosylation catalyst.

bioRxiv : the preprint server for biology·2026
Same journal

Unlocking the capacity of Mn-based Prussian blue cathodes in capacitive deionization.

Nature communications·2026
Same journal

Scaling biodiversity-stability relationships from populations to meta-communities across trophic levels.

Nature communications·2026
Same journal

Thermodynamically programmed one-pot CRISPR platform for point-of-care SNP genotyping.

Nature communications·2026
Same journal

Engineering all-organic electrocatalysts with asymmetric dual-active sites for uncommon oxygen-evolving pathway.

Nature communications·2026
Same journal

Rapid GC content evolution in rice through GC-biased gene conversion and selection for translation efficiency.

Nature communications·2026
Same journal

Declines in organic matter persistence with increased soil carbon.

Nature communications·2026
See all related articles
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 Experiment Video

Updated: May 13, 2025

Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions
06:50

Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions

Published on: January 26, 2024

913

Programmable protein stabilization with language model-derived peptide guides.

Lauren Hong1, Tianzheng Ye2, Tian Z Wang1

  • 1Department of Biomedical Engineering, Duke University, Durham, NC, USA.

Nature Communications
|April 14, 2025
PubMed
Summary
This summary is machine-generated.

Researchers engineered novel deubiquibodies (duAbs) to stabilize proteins, expanding targeted protein stabilization (TPS) for diseases like cancer. This approach targets previously undruggable proteins, including tumor suppressors and fusion oncoproteins.

More Related Videos

Residue-Specific Exchange of Proline by Proline Analogs in Fluorescent Proteins: How "Molecular Surgery" of the Backbone Affects Folding and Stability
10:31

Residue-Specific Exchange of Proline by Proline Analogs in Fluorescent Proteins: How "Molecular Surgery" of the Backbone Affects Folding and Stability

Published on: February 3, 2022

2.9K
Constructing Cyclic Peptides Using an On-Tether Sulfonium Center
07:11

Constructing Cyclic Peptides Using an On-Tether Sulfonium Center

Published on: September 28, 2022

2.6K

Related Experiment Videos

Last Updated: May 13, 2025

Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions
06:50

Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions

Published on: January 26, 2024

913
Residue-Specific Exchange of Proline by Proline Analogs in Fluorescent Proteins: How "Molecular Surgery" of the Backbone Affects Folding and Stability
10:31

Residue-Specific Exchange of Proline by Proline Analogs in Fluorescent Proteins: How "Molecular Surgery" of the Backbone Affects Folding and Stability

Published on: February 3, 2022

2.9K
Constructing Cyclic Peptides Using an On-Tether Sulfonium Center
07:11

Constructing Cyclic Peptides Using an On-Tether Sulfonium Center

Published on: September 28, 2022

2.6K

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Drug Discovery

Background:

  • Dysregulated protein degradation via the ubiquitin-proteasomal pathway is implicated in diseases such as cancer, neurodegeneration, and diabetes.
  • Current targeted protein stabilization (TPS) and targeted protein degradation (TPD) platforms require structured binding pockets, limiting their application to "undruggable" targets.
  • There is a need for novel therapeutic strategies to address protein dysregulation in diseases with limited treatment options.

Purpose of the Study:

  • To expand the scope of targeted protein stabilization (TPS) by developing a novel platform for stabilizing proteins lacking traditional binding pockets.
  • To engineer deubiquibodies (duAbs) by fusing computationally designed peptides to the OTUB1 deubiquitinase catalytic domain.
  • To demonstrate the efficacy of duAbs in stabilizing diverse protein targets, including tumor suppressors and fusion oncoproteins, and their potential for therapeutic applications.

Main Methods:

  • Computational design of peptides targeting specific proteins using protein language models.
  • Fusion of designed peptides to the catalytic domain of OTUB1 to create deubiquibodies (duAbs).
  • Validation of duAb-mediated protein stabilization in human cells, assessing deubiquitinase (DUB) dependence.
  • Engineering duAbs against conformationally diverse targets like p53, WEE1, and PAX3::FOXO1.
  • Encapsulation of p53-targeting duAb mRNA in lipid nanoparticles for intracellular delivery.

Main Results:

  • Engineered duAbs effectively stabilize exogenous and endogenous proteins in a DUB-dependent manner.
  • DuAbs were successfully engineered to target conformationally diverse proteins, including tumor suppressors (p53, WEE1) and disordered fusion oncoproteins (PAX3::FOXO1).
  • mRNA-encapsulated p53-targeting duAbs demonstrated effective intracellular delivery, p53 stabilization, and apoptosis activation in cellular models.

Conclusions:

  • Deubiquibodies (duAbs) represent a novel platform for targeted protein stabilization (TPS), overcoming limitations of traditional drug design.
  • This approach expands the druggable proteome, offering potential therapeutic strategies for diseases driven by protein dysregulation.
  • The successful in vitro demonstration of mRNA-delivered duAbs warrants further investigation for in vivo translation and clinical development.