Related Experiment Video

Updated: Jun 21, 2026

Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry
05:53

Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry

Published on: June 21, 2018

Disorder, promiscuity, and toxic partnerships

Edward M Marcotte1, Mark Tsechansky

  • 1Department of Chemistry and Biochemistry, University of Texas at Austin, 2500 Speedway, Austin, TX 78712-1064, USA. marcotte@icmb.utexas.edu

Cell
|July 15, 2009
PubMed

Insights

Overexpressed genes can be toxic, but the reasons are unclear. This study reveals that protein disorder and promiscuous interactions determine gene dosage sensitivity, explaining oncogene toxicity.

Area of Science:

  • Genetics
  • Molecular Biology
  • Biochemistry

Background:

  • Gene overexpression can lead to cellular toxicity, a phenomenon observed across various organisms.
  • The underlying molecular mechanisms driving this gene dosage sensitivity have remained largely unexplained.
  • Dosage-sensitive genes, when present in abnormal copy numbers, can disrupt cellular homeostasis.

Discussion:

  • Intrinsic protein disorder and promiscuous molecular interactions are identified as key factors contributing to gene dosage sensitivity.
  • These properties allow proteins to interact with a wider range of cellular components, increasing the likelihood of detrimental interactions upon overexpression.
  • This mechanism provides a partial explanation for the toxicity observed in dosage-sensitive oncogenes.

Key Insights:

  • Proteins with intrinsically disordered regions are more prone to dosage sensitivity.
  • Promiscuous protein interactions exacerbate the negative effects of gene overexpression.
  • These findings offer a mechanistic link between protein properties and gene toxicity.

Outlook:

  • Further research can explore the role of protein disorder and interaction promiscuity in other genetic disorders.
  • Therapeutic strategies could target protein interactions to mitigate the toxicity of overexpressed genes.
  • Understanding these mechanisms may aid in the development of novel cancer therapies targeting oncogene addiction.

More Related Videos

High-throughput Identification of Synergistic Drug Combinations by the Overlap2 Method07:51

High-throughput Identification of Synergistic Drug Combinations by the Overlap2 Method

Published on: May 21, 2018

Related Concept Videos

Pharmacogenomics: Identification of New Drug Targets01:29

Pharmacogenomics: Identification of New Drug Targets

Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...
Pharmacogenetics and Pharmacogenomics: Overview01:29

Pharmacogenetics and Pharmacogenomics: Overview

Pharmacogenetics and pharmacogenomics examine how genetic factors influence an individual's response to drugs. While pharmacogenetics focuses on the impact of specific genetic variants on drug effects, pharmacogenomics takes a broader approach, studying how genetic variation across populations contributes to differences in drug responses. These fields aim to explain why individuals may experience varying levels of efficacy or adverse reactions to the same medication.Variability in drug...
Sex Linked Disorders01:43

Sex Linked Disorders

Like autosomes, sex chromosomes contain a variety of genes necessary for normal body function. When a mutation in one of these genes results in biological deficits, the disorder is considered sex-linked.
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...
Genomics02:02

Genomics

Genomics is the science of genomes: it is the study of all the genetic material of an organism. In humans, the genome consists of information carried in 23 pairs of chromosomes in the nucleus, as well as mitochondrial DNA. In genomics, both coding and non-coding DNA is sequenced and analyzed. Genomics allows a better understanding of all living things, their evolution, and their diversity. It has a myriad of uses: for example, to build phylogenetic trees, to improve productivity and...
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...