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

Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu01:29

Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu

Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
Principles of Pharmacogenetics: Types of Genetic Variants01:27

Principles of Pharmacogenetics: Types of Genetic Variants

The human genome is over 99.9% identical between individuals, yet genetic differences exist at millions of bases. The human genome contains approximately 3 million variant positions per individual, many of which are heterozygous, contributing to genetic diversity and individual traits. Genetic variations include single-nucleotide polymorphisms (SNPs), insertions, deletions, and copy number variations (CNVs).SNPs, the most common variation, involve single-base changes in DNA. These can be...
Pharmacogenetics of Drug Metabolism: Overview01:27

Pharmacogenetics of Drug Metabolism: Overview

Genetic polymorphism in drug metabolism is crucial to the inter-individual variability observed in drug responses. Drug metabolism primarily involves the chemical modification of drugs and other xenobiotics to enhance their elimination by increasing their polarity. Two main classes of enzymes mediate this biotransformation process: Phase I enzymes, primarily cytochrome P450s, catalyze oxidation and reduction reactions, while other enzymes, such as esterases, mediate hydrolysis, and Phase II...
Human Genetics01:28

Human Genetics

Human genetics provides a profound framework for understanding the interplay between genetic predispositions and human psychology. At the heart of this discipline lies the study of how genes influence physical traits, behaviors, and susceptibility to diseases. Each person carries a unique genetic code that subtly or significantly shapes their psychological and behavioral landscape.
The complex relationship between genetics and psychology is observable through common biological components such...
Pleiotropy01:33

Pleiotropy

Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...

You might also read

Related Articles

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

Sort by
Same author

Disruption of androgen receptor-cofactor interactions by the RNA-binding protein FUS/TLS alters androgen signalling in prostate cancer.

Oncogene·2026
Same author

Thieno[2,3-<i>b</i>]pyridine compounds potently inhibit prostate cancer growth and motility.

Endocrine oncology (Bristol, England)·2025
Same author

Understanding limb necrotizing infections: A comprehensive approach.

Revista espanola de cirugia ortopedica y traumatologia·2024
Same author

Understanding limb necrotizing infections: A comprehensive approach.

Revista espanola de cirugia ortopedica y traumatologia·2024
Same author

[Translated article] Clinical results of total hip arthroplasty assisted by robotic arm in Spain: Preliminary study.

Revista espanola de cirugia ortopedica y traumatologia·2023
Same author

MAPK11 (p38β) is a major determinant of cellular radiosensitivity by controlling ionizing radiation-associated senescence: An in vitro study.

Clinical and translational radiation oncology·2023

Related Experiment Video

Updated: Jun 19, 2026

High-resolution Melting PCR for Complement Receptor 1 Length Polymorphism Genotyping: An Innovative Tool for Alzheimer's Disease Gene Susceptibility Assessment
07:26

High-resolution Melting PCR for Complement Receptor 1 Length Polymorphism Genotyping: An Innovative Tool for Alzheimer's Disease Gene Susceptibility Assessment

Published on: July 18, 2017

HEY1 Leu94Met gene polymorphism dramatically modifies its biological functions.

M A Villaronga1, D N Lavery, C L Bevan

  • 1Department of Cancer Biology, Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, 28029 Madrid, Spain.

Oncogene
|October 6, 2009
PubMed
Summary

A common HEY1 gene variant (Leu94Met) alters its function, changing it from a tumor suppressor regulator to a potential cancer promoter by affecting androgen receptor and p53 activity.

More Related Videos

An Allele-specific Gene Expression Assay to Test the Functional Basis of Genetic Associations
10:17

An Allele-specific Gene Expression Assay to Test the Functional Basis of Genetic Associations

Published on: November 3, 2010

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
09:34

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease

Published on: April 4, 2018

Related Experiment Videos

Last Updated: Jun 19, 2026

High-resolution Melting PCR for Complement Receptor 1 Length Polymorphism Genotyping: An Innovative Tool for Alzheimer's Disease Gene Susceptibility Assessment
07:26

High-resolution Melting PCR for Complement Receptor 1 Length Polymorphism Genotyping: An Innovative Tool for Alzheimer's Disease Gene Susceptibility Assessment

Published on: July 18, 2017

An Allele-specific Gene Expression Assay to Test the Functional Basis of Genetic Associations
10:17

An Allele-specific Gene Expression Assay to Test the Functional Basis of Genetic Associations

Published on: November 3, 2010

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
09:34

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease

Published on: April 4, 2018

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • HEY1 (hairy/enhancer-of-split related with YRPW motif 1) is a transcriptional repressor involved in Notch signaling.
  • HEY1 regulates cancer-related pathways, including p53 tumor suppressor and androgen receptor activity.
  • A naturally occurring HEY1 polymorphism (Leu94Met) is investigated for its functional impact.

Purpose of the Study:

  • To investigate how the HEY1 Leu94Met polymorphism alters its function as a transcriptional regulator.
  • To determine the impact of this polymorphism on androgen receptor and p53 pathway interactions.
  • To analyze the functional consequences of the Leu94Met variant in cellular processes and drug sensitivity.

Main Methods:

  • Functional analysis of HEY1 and its Leu94Met variant in human osteosarcoma U2OS cells.
  • Assessment of androgen receptor co-repression/co-activation activity.
  • Evaluation of p53-mediated cell-cycle arrest and differentiation.
  • Analysis of subcellular localization motifs and their mutation effects.

Main Results:

  • The HEY1 Leu94Met polymorphism converts the protein from an androgen receptor corepressor to a coactivator.
  • This variant abolishes HEY1-mediated p53 activation, suppressing p53-dependent cell-cycle arrest and differentiation.
  • HEY1, but not the Leu94Met variant, confers sensitivity to p53-activating chemotherapeutic drugs.
  • Specific motifs critical for HEY1 subcellular localization and function were identified and mutated.

Conclusions:

  • The HEY1 Leu94Met polymorphism significantly alters its biological activities, impacting its roles in oncogenic processes.
  • This variant may represent a key factor in cancer development or progression by modulating critical cellular pathways.
  • Understanding HEY1 polymorphism is crucial for evaluating its role in cancer and response to therapy.