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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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Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
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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.
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Related Experiment Video

Updated: Apr 16, 2026

Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates
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YY1 positively regulates human UBIAD1 expression.

Nobuaki Funahashi1, Yoshihisa Hirota2, Kimie Nakagawa3

  • 1Department of Hygienic Sciences, Kobe Pharmaceutical University, Kobe, Japan; Department of Metabolic Disorder, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.

Biochemical and Biophysical Research Communications
|March 17, 2015
PubMed
Summary

The transcription factor YY1 regulates the expression of UBIAD1, an enzyme crucial for menaquinone-4 (MK-4) biosynthesis. This finding sheds light on the regulation of vitamin K2 production and its potential role in cancer.

Keywords:
Gene regulationUBIAD1Vitamin KYY1

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siRNA Screening to Identify Ubiquitin and Ubiquitin-like System Regulators of Biological Pathways in Cultured Mammalian Cells
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Profiling Ubiquitin and Ubiquitin-like Dependent Post-translational Modifications and Identification of Significant Alterations
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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Genetics

Background:

  • Vitamin K is essential for bone health and blood clotting, with natural forms including phylloquinone (K1) and menaquinones (K2).
  • Menaquinone-4 (MK-4) is a bioactive form of vitamin K2, and its biosynthetic enzyme is UbiA prenyltransferase domain containing 1 (UBIAD1).
  • UBIAD1 expression is altered in prostate cancer, suggesting a role in tumorigenesis, but its gene regulation remains unclear.

Purpose of the Study:

  • To elucidate the regulatory mechanisms of the human UBIAD1 gene.
  • To identify transcription factors that control UBIAD1 expression.
  • To understand the functional significance of UBIAD1 regulation in cellular processes.

Main Methods:

  • Cloning and characterization of the human UBIAD1 promoter region.
  • 5' rapid amplification of cDNA ends (RACE) to identify the transcriptional start site.
  • Deletion and mutation analyses of the promoter to identify functional motifs.
  • Electrophoretic gel mobility shift assays (EMSA) and chromatin immunoprecipitation (ChIP) assays to study protein-DNA interactions.
  • Small interfering RNA (siRNA) knockdown of YY1 to assess its effect on UBIAD1 expression and activity.

Main Results:

  • The primary transcriptional start site of the human UBIAD1 gene was mapped.
  • The YY1 consensus motif within the UBIAD1 promoter was identified as functionally important.
  • Electrophoretic gel mobility shift and chromatin immunoprecipitation assays confirmed that YY1 binds to the UBIAD1 promoter both in vitro and in vivo.
  • Knockdown of YY1 using siRNA led to decreased UBIAD1 mRNA expression and reduced UBIAD1 conversion activity.

Conclusions:

  • The transcription factor YY1 up-regulates the expression of the UBIAD1 gene.
  • YY1 also enhances UBIAD1's menaquinone-4 conversion activity via the UBIAD1 promoter.
  • These findings reveal a key regulatory pathway for UBIAD1 and provide insights into vitamin K2 biosynthesis.