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Related Concept Videos

Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

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Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
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Peptide Bonds02:43

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A peptide bond covalently attaches amino acids through a dehydration reaction. One amino acid's carboxyl group and another amino acid's amino group combine, releasing a water molecule. The resulting bond is the peptide bond. The products that such linkages form are peptides. As more amino acids join this growing chain, the resulting chain is a polypeptide. Each polypeptide has a free amino group at one end. This end has the N-terminal, or the amino-terminal, and the other end has a free...
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Nuclear Fusion02:45

Nuclear Fusion

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The process of converting very light nuclei into heavier nuclei is also accompanied by the conversion of mass into large amounts of energy, a process called fusion. The principal source of energy in the sun is a net fusion reaction in which four hydrogen nuclei fuse and ultimately produce one helium nucleus and two positrons.
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Transcription Factors02:16

Transcription Factors

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Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
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Repressed Memory01:16

Repressed Memory

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Repressed memories are a psychological phenomenon where memories of traumatic events are unconsciously blocked from a person's awareness. This process occurs as a defense mechanism, protecting the mind from the emotional impact of distressing or painful experiences. For example, a person who has experienced childhood trauma may grow up with no conscious recollection of the event. In such cases, the memories are thought to be buried deep within the subconscious, inaccessible to the conscious...
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Eukaryotic Transcription Activators02:42

Eukaryotic Transcription Activators

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Transcription activators are proteins that promote the transcription of genes from DNA to RNA. In most cases, these proteins contain two separate domains ‒ a domain that binds to DNA and a domain for activating transcription; however, in some cases, a single domain is responsible for both binding and activation of transcription, as seen in the glucocorticoid receptor and MyoD.
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Related Experiment Video

Updated: Feb 9, 2026

Analysis of SNARE-mediated Membrane Fusion Using an Enzymatic Cell Fusion Assay
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CPP-E1A fusion peptides inhibit CtBP-mediated transcriptional repression.

Melanie A Blevins1, Caiguo Zhang2, Lingdi Zhang1

  • 1Department of Biochemistry and Molecular Genetics, University of Colorado Denver Anschutz Medical Campus, Aurora, CO, USA.

Molecular Oncology
|June 8, 2018
PubMed
Summary

Researchers developed cell-penetrating peptides (CPPs) fused with PXDLS motifs to inhibit carboxyl-terminal binding proteins (CtBP). These peptides disrupt CtBP

Keywords:
CtBPCtBP inhibitorscell-penetrating peptidestranscriptional corepressors

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Area of Science:

  • Molecular Biology
  • Cancer Research
  • Drug Discovery

Background:

  • Carboxyl-terminal binding proteins (CtBP) are transcriptional corepressors overexpressed in cancers.
  • CtBP promotes epithelial-to-mesenchymal transition, stemness, and survival, and drives p53-independent apoptosis upon knockdown.
  • CtBPs interact with transcription factors via a conserved PXDLS peptide motif.

Purpose of the Study:

  • To investigate the feasibility of using PXDLS-motif-containing peptides fused to cell-penetrating peptides (CPPs) to inhibit CtBP function.
  • To explore CPP-fused PXDLS peptides as potential therapeutic agents targeting CtBP in cancer.

Main Methods:

  • Designed and synthesized PXDLS-motif-containing peptides fused to CPPs.
  • Utilized AlphaScreen assays to assess CtBP-protein partner interaction disruption.
  • Evaluated peptide cellular uptake in lung carcinoma and melanoma cells.
  • Assessed inhibition of CtBP-mediated transcriptional repression.
  • Investigated the in vivo and in vitro effects of a specific peptide (Pep1-E1A-WT) on melanoma cell phenotypes and tumor growth.

Main Results:

  • CPP-fused PXDLS peptides successfully disrupted CtBP interaction with its partner E1A in vitro.
  • Peptides demonstrated cellular penetration in lung carcinoma and melanoma cells.
  • Disruption of CtBP-transcription factor interaction and inhibition of CtBP-mediated repression were observed.
  • Constitutive expression of Pep1-E1A-WT reversed oncogenic phenotypes and limited tumor growth in vivo.

Conclusions:

  • CPP-fused PXDLS peptides are effective in disrupting CtBP function and inhibiting CtBP-mediated oncogenic pathways.
  • These peptides represent a promising strategy for developing novel research tools or therapeutic agents against CtBP-driven cancers.
  • Further development of these peptides could target various biological pathways regulated by CtBP.