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

Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

2.3K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.3K
Nuclear Protein Sorting01:34

Nuclear Protein Sorting

4.4K
Nuclear protein sorting is the selective trafficking of histones, polymerases, gene regulatory proteins into the nucleus and exporting RNAs and ribosomes to the cytosol. It is a tightly controlled process that regulates gene expression within a cell.
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
4.4K
Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

3.4K
After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
3.4K
Nuclear Export of mRNA02:31

Nuclear Export of mRNA

7.5K
Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
7.5K
The Unfolded Protein Response01:37

The Unfolded Protein Response

4.3K
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
4.3K
Protein Translocation Machinery on the ER Membrane01:28

Protein Translocation Machinery on the ER Membrane

4.3K
The translocon complex situated on the ER membrane is the main gateway for the protein secretory pathway. It facilitates the transport of nascent peptides into the ER lumen and their insertion into the ER membrane.
Sec61 protein conducting channel
In eukaryotes, the translocon complex comprises a core heterotrimeric translocator channel called the Sec61 complex. This channel includes three transmembrane proteins, Sec61α, Sec61β, and Sec61γ, and is the largest subunit of the...
4.3K

You might also read

Related Articles

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

Sort by
Same author

Case of Basal Cell Prostate Cancer and Recurrence With Prostatic Adenocarcinoma in a United States Military Veteran Exposed to Agent Orange.

Clinical case reports·2026
Same author

Structure-Based Discovery of Potent BCL-XL Inhibitors through Rescaffolding.

Journal of medicinal chemistry·2026
Same author

Large scale functional and effective connectivity alterations cross the Huntington's disease integrated staging system.

NeuroImage. Clinical·2026
Same author

Genome-Wide Identification of Pineapple AcINH Genes and Functional Characterization of <i>AcINH3</i> in Sucrose Metabolism and Drought Tolerance.

Plants (Basel, Switzerland)·2026
Same author

Guideline for the Diagnosis and Management of Heritable IFNAR1 Deficiency in Oceania.

Journal of paediatrics and child health·2026
Same author

Rare Postoperative Pelvic Lymphocyst Infection by <i>Streptococcus mitis/oralis</i>: A Case Study.

International medical case reports journal·2026

Related Experiment Video

Updated: May 17, 2025

Assays for the Degradation of Misfolded Proteins in Cells
10:56

Assays for the Degradation of Misfolded Proteins in Cells

Published on: August 28, 2016

11.9K

Chemically Induced Nuclear Pore Complex Protein Degradation via TRIM21.

Xiaomei Li1, Qingyang Wang1, Anping Guo1

  • 1HitGen Inc., Chengdu, Sichuan 610200, China.

ACS Chemical Biology
|April 18, 2025
PubMed
Summary

Researchers discovered new small-molecule ligands for the TRIM21 E3 ligase using DNA-Encoded Library technology. These ligands degrade nuclear pore complex proteins, leading to cancer cell death via nuclear envelope disruption.

More Related Videos

Cycloheximide Chase Analysis of Protein Degradation in Saccharomyces cerevisiae
09:05

Cycloheximide Chase Analysis of Protein Degradation in Saccharomyces cerevisiae

Published on: April 18, 2016

28.8K
High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines
05:33

High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines

Published on: November 9, 2020

9.3K

Related Experiment Videos

Last Updated: May 17, 2025

Assays for the Degradation of Misfolded Proteins in Cells
10:56

Assays for the Degradation of Misfolded Proteins in Cells

Published on: August 28, 2016

11.9K
Cycloheximide Chase Analysis of Protein Degradation in Saccharomyces cerevisiae
09:05

Cycloheximide Chase Analysis of Protein Degradation in Saccharomyces cerevisiae

Published on: April 18, 2016

28.8K
High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines
05:33

High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines

Published on: November 9, 2020

9.3K

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Drug Discovery

Background:

  • Bifunctional degrader molecules, like proteolysis-targeting chimeras (PROTACs), show promise but are limited by a scarcity of E3 ligase ligands.
  • TRIM21 is an E3 ligase with potential therapeutic applications.

Purpose of the Study:

  • To identify novel small-molecule ligands for the E3 ligase TRIM21.
  • To investigate the mechanism of action and cellular effects of these TRIM21 ligands.

Main Methods:

  • DNA-Encoded Library (DEL) technology for ligand discovery.
  • Crystallography to confirm ligand-TRIM21 interaction.
  • Proteomic studies to identify protein targets.
  • Immunofluorescence assays to assess cellular effects.

Main Results:

  • Identified novel small-molecule ligands for TRIM21.
  • Demonstrated antiproliferative effects of ligands across cancer cell types.
  • Discovered that ligands downregulate Nuclear Pore Complex Protein NUP155 and mRNA Export Factor GLE1 in a TRIM21-dependent, ubiquitin-proteasome pathway.
  • Showed NUP155 is the primary target, with GLE1 as a passenger target.
  • Confirmed degradation of NUP155 and GLE1 disrupts nuclear envelope integrity, causing cell death.

Conclusions:

  • Novel TRIM21 ligands were discovered using DEL technology.
  • TRIM21 ligands act as monovalent degraders, inducing degradation of NUP155 and GLE1.
  • Degradation of these proteins leads to nuclear envelope disruption and cell death, revealing a new mode of action for TRIM21 ligands.