Related Experiment Video

Updated: Jul 2, 2026

Inducible and Reversible Dominant-negative (DN) Protein Inhibition
08:35

Inducible and Reversible Dominant-negative (DN) Protein Inhibition

Published on: January 7, 2019

Deletion analysis and alternative splicing define a transactivation inhibitory domain in human oncoprotein REL

J R Leeman1, M A Weniger, T F Barth

  • 1Department of Biology, Boston University, Boston, MA 02215, USA.

Oncogene
|August 13, 2008
PubMed

Insights

Researchers identified a REL inhibitory domain (RID) that regulates REL transcription factor activity. A specific REL splice variant, RELDelta9, is elevated in lymphoma, suggesting its potential as a diagnostic marker for lymphoid tumors.

Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • The transcription factor REL, a member of the nuclear factor-kappaB family, is implicated in human lymphoid malignancies.
  • REL contains a Rel homology domain (RHD) for DNA binding/dimerization and a C-terminal transactivation domain (TAD).

Purpose of the Study:

  • To define a novel inhibitory domain within REL and characterize its role in transcription factor regulation.
  • To investigate the functional significance of REL mRNA splice variants, specifically RELDelta9 and REL+Alu, in lymphoid malignancies.

Main Methods:

  • Deletion analysis to identify and characterize the REL inhibitory domain (RID).
  • Functional assays (e.g., GAL4-REL transactivation) to assess the impact of RID and splice variants on REL activity.
  • Reverse transcriptase-polymerase chain reaction (RT-PCR) to analyze REL mRNA expression in lymphoma samples and cell lines.

Main Results:

  • Deletion of the REL inhibitory domain (RID, amino acids 323-422) significantly increases REL transactivation and DNA binding.
  • Two REL mRNA splice variants, RELDelta9 (lacking exon 9) and REL+Alu (with Alu insertion), were identified.
  • Both RID deletion and exon 9 deletion enhance REL transactivation and DNA binding.
  • The RELDelta9 splice variant is preferentially expressed in lymphoma tissues and cell lines.

Conclusions:

  • The identified REL inhibitory domain (RID) plays a crucial role in modulating REL's transcriptional activity and DNA binding.
  • The RELDelta9 splice variant's preferential expression in lymphoma suggests it can serve as a potential biomarker for lymphoid tumors.
  • Understanding REL regulation and its splice variants offers insights into lymphoid malignancies and potential diagnostic strategies.

More Related Videos

Detection of Alternative Splicing During Epithelial-Mesenchymal Transition11:48

Detection of Alternative Splicing During Epithelial-Mesenchymal Transition

Published on: October 9, 2014

Investigation of the Transcriptional Role of a RUNX1 Intronic Silencer by CRISPR/Cas9 Ribonucleoprotein in Acute Myeloid Leukemia Cells09:16

Investigation of the Transcriptional Role of a RUNX1 Intronic Silencer by CRISPR/Cas9 Ribonucleoprotein in Acute Myeloid Leukemia Cells

Published on: September 1, 2019

Related Concept Videos

Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
Alternative RNA Splicing02:18

Alternative RNA Splicing

Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
Alternative RNA Splicing02:18

Alternative RNA Splicing

Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
RNA Polymerase II Accessory Proteins02:36

RNA Polymerase II Accessory Proteins

Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...