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

Mutagenicity and Carcinogenicity01:25

Mutagenicity and Carcinogenicity

1.3K
Mutagenicity and carcinogenicity refer to the ability of drugs to cause genetic defects and induce cancer, respectively. The International Agency for Research on Cancer (IARC) classifies agents into four groups based on their carcinogenic potential. Group 1 agents are known human carcinogens; group 2A agents are probably carcinogenic to humans; group 3 agents lack data to support their role in carcinogenesis; and group 4 includes agents for which data support that they are not likely to be...
1.3K
Lethal Alleles02:41

Lethal Alleles

15.6K
Agouti: A Lethal Allele
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
15.6K
Cancer-Critical Genes I: Proto-oncogenes01:33

Cancer-Critical Genes I: Proto-oncogenes

9.1K
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
9.1K
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

5.0K
Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
5.0K
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

6.9K
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....
6.9K
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

7.7K
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
7.7K

You might also read

Related Articles

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

Sort by
Same author

Structure of the NAT10 acetyltransferase and mechanism of tRNA acetylation.

Nature communications·2026
Same author

Discovery of a [4Fe-4S] cluster in the PRRSV Nsp1α leader protease reveals host-virus interplay in its downstream functions.

Science advances·2026
Same author

Trans-kingdom coupling of redox signaling to environmental cell stress responses through multiphase partitioning.

bioRxiv : the preprint server for biology·2026
Same author

Hierarchical small molecule inhibition of MYST acetyltransferases.

Nature communications·2026
Same author

Integrated computational and experimental immunoengineering of adeno-associated virus capsid T cell epitopes in mice.

Nature communications·2026
Same author

A phage protein screen identifies triggers of the bacterial innate immune system.

Nature microbiology·2026
Same journal

Lipid Metabolic Labeling to Study Site- and Lipid-Specific Long-Chain <i>S</i>-Acylation Dynamics.

ACS chemical biology·2026
Same journal

Inositol Thiophosphates as Inhibitors of Mammalian, Plant, and Fungal Phytases.

ACS chemical biology·2026
Same journal

Synthesis and Characterization of the Spectroscopic and Imaging Utilities of Two Indole-Based Cyan Fluorescent Nucleoside Analogues.

ACS chemical biology·2026
Same journal

Indole Ring Expansion and Rearrangement-Enabled Quinoline Scaffold Formation in the Biosynthesis of the Antitumor Monoterpene Indole Alkaloid Camptothecin.

ACS chemical biology·2026
Same journal

Intracellular Delivery of Peptides and Proteins with an Engineered Membrane Translocation Domain.

ACS chemical biology·2026
Same journal

Development of Next-Generation Fluoroacetamidine-Containing Activity-Based Probes for the Selective Labeling of the Protein Arginine Deiminases (PADs).

ACS chemical biology·2026
See all related articles

Related Experiment Video

Updated: Aug 26, 2025

A Data Integration Workflow to Identify Drug Combinations Targeting Synthetic Lethal Interactions
07:40

A Data Integration Workflow to Identify Drug Combinations Targeting Synthetic Lethal Interactions

Published on: May 27, 2021

4.2K

Conditional Covalent Lethality Driven by Oncometabolite Accumulation.

Minervo Perez1, Kellie D Nance1, Daniel W Bak2

  • 1Chemical Biology Laboratory, National Cancer Institute, Frederick, Maryland 21072, United States.

ACS Chemical Biology
|October 3, 2022
PubMed
Summary
This summary is machine-generated.

Researchers discovered a new way to target cancer by exploiting the unique metabolic vulnerabilities in Hereditary leiomyomatosis and renal cell carcinoma (HLRCC). A novel covalent molecule, MP-1, selectively kills cancer cells with fumarate hydratase (FH) mutations.

More Related Videos

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

13.3K
Efficient Purification and LC-MS/MS-based Assay Development for Ten-Eleven Translocation-2 5-Methylcytosine Dioxygenase
10:33

Efficient Purification and LC-MS/MS-based Assay Development for Ten-Eleven Translocation-2 5-Methylcytosine Dioxygenase

Published on: October 15, 2018

8.3K

Related Experiment Videos

Last Updated: Aug 26, 2025

A Data Integration Workflow to Identify Drug Combinations Targeting Synthetic Lethal Interactions
07:40

A Data Integration Workflow to Identify Drug Combinations Targeting Synthetic Lethal Interactions

Published on: May 27, 2021

4.2K
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

13.3K
Efficient Purification and LC-MS/MS-based Assay Development for Ten-Eleven Translocation-2 5-Methylcytosine Dioxygenase
10:33

Efficient Purification and LC-MS/MS-based Assay Development for Ten-Eleven Translocation-2 5-Methylcytosine Dioxygenase

Published on: October 15, 2018

8.3K

Area of Science:

  • Biochemistry
  • Oncology
  • Chemical Biology

Background:

  • Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a cancer predisposition syndrome caused by mutations in the fumarate hydratase (FH) tumor suppressor gene.
  • FH inactivation leads to the accumulation of the electrophilic oncometabolite fumarate, creating unique metabolic vulnerabilities.
  • Targeting tumor suppressors often involves identifying synthetic lethal interactions, especially when direct reactivation is not feasible.

Purpose of the Study:

  • To investigate whether the electrophilic nature of the HLRCC metabolome creates susceptibility to covalent small molecules, termed conditional covalent lethality.
  • To identify novel therapeutic strategies for HLRCC by screening for FH-dependent cytotoxicity.
  • To explore the potential of chemoproteomic methods for identifying functional oncometabolite targets.

Main Methods:

  • Screening a diverse panel of electrophilic small molecules to identify compounds with FH-dependent cytotoxicity.
  • Synthesizing and performing structure-activity relationship (SAR) profiling of identified covalent ligands.
  • Utilizing chemoproteomic profiling with clickable probes to identify protein targets and cysteine reactivity.
  • Assessing the role of identified targets, such as TRMT1, in mediating the compound's effects.

Main Results:

  • A covalent ligand, MP-1, was identified that exhibits significant FH-dependent cytotoxicity.
  • SAR studies elucidated key molecular features responsible for MP-1's activity.
  • Chemoproteomic analysis confirmed MP-1 engages multiple functional cysteines, including one in the tRNA methyltransferase TRMT1.
  • TRMT1 overexpression partially rescued tRNA methylation and attenuated MP-1's cytotoxicity, implicating TRMT1 as a key target.

Conclusions:

  • The study demonstrates the potential of exploiting metabolic vulnerabilities with covalent small molecules for targeted cancer therapy in HLRCC.
  • Conditional covalent lethality represents a promising strategy for developing novel cancer therapeutics.
  • Phenotypic screening combined with chemoproteomic target identification can uncover new functional oncometabolite targets and therapeutic avenues.