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Related Concept Videos

Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

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The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
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Constitutive and Regulated Gene Expression01:27

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Gene expression in prokaryotes is governed by constitutive and regulated systems, allowing cells to balance the production of essential proteins with adaptive responses to environmental changes.Constitutive Gene ExpressionConstitutive, or housekeeping, genes are continuously expressed as they encode proteins vital for fundamental cellular processes. These include enzymes for glycolysis, ribosomal components for protein synthesis, and proteins involved in DNA replication. Their constant...
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Combinatorial Gene Control02:33

Combinatorial Gene Control

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Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
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Genetic Screens02:46

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Genetic screens are tools used to identify genes and mutations responsible for phenotypes of interest. Genetic screens help identify individuals or a group of people at risk of developing  genetic diseases and help them with early intervention, targeted therapy, and reproductive options.
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Cell Specific Gene Expression01:58

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Related Experiment Video

Updated: Jul 22, 2025

Inherent Dynamics Visualizer, an Interactive Application for Evaluating and Visualizing Outputs from a Gene Regulatory Network Inference Pipeline
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Orphan quality control shapes network dynamics and gene expression.

Kevin G Mark1, SriDurgaDevi Kolla1, Jacob D Aguirre2

  • 1Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, CA, USA.

Cell
|July 21, 2023
PubMed
Summary
This summary is machine-generated.

The E3 ligase UBR5 degrades unpaired transcription factor subunits, establishing dynamic protein networks essential for cell fate decisions and gene expression. This orphan quality control mechanism maintains cellular responsiveness to environmental signals.

Keywords:
MCRS1MYCUBR5branched ubiquitin chainorphan quality controlproteasomestem celltranscription factorubiquitin

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Area of Science:

  • Molecular biology
  • Cellular signaling
  • Protein degradation pathways

Background:

  • Eukaryotic cells rely on complex protein networks for cell fate determination.
  • Dysfunctional protein interactions in these networks are linked to various diseases.
  • The mechanisms governing the composition and dynamics of these networks are not fully understood.

Purpose of the Study:

  • To identify signaling hubs that regulate the composition and dynamics of transcriptional regulatory networks.
  • To investigate the role of the E3 ligase UBR5 in protein network homeostasis.
  • To understand how protein degradation contributes to dynamic gene expression.

Main Methods:

  • Biochemical assays to characterize protein-protein interactions.
  • Structural analyses to determine binding interfaces.
  • Investigating the role of UBR5 in regulating transcriptional regulators, including those associated with c-Myc.

Main Results:

  • UBR5 identified as a signaling hub that degrades unpaired subunits of transcriptional regulators.
  • UBR5 binds to specific motifs exposed only after complex dissociation.
  • Rapid turnover of unpaired subunits by UBR5 promotes dynamic protein interactions.

Conclusions:

  • Orphan quality control, mediated by UBR5, is crucial for establishing dynamic protein networks.
  • This process allows cells to balance gene expression with environmental responsiveness.
  • Understanding UBR5's role offers potential therapeutic strategies for diseases linked to aberrant gene expression.