Related Experiment Video

Updated: Oct 9, 2025

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
10:51

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists

Published on: November 15, 2013

12.9K

The Transcriptional Repressor Orphan Nuclear Receptor TLX Is Responsive to Xanthines

Giuseppe Faudone1, Whitney Kilu1, Xiaomin Ni1,2

  • 1Institute of Pharmaceutical Chemistry, Goethe University Frankfurt, Max-von-Laue-Str. 9, D-60438 Frankfurt, Germany.

ACS Pharmacology & Translational Science
|December 20, 2021
PubMed

Insights

Xanthines like caffeine modulate the tailless homologue (TLX) receptor, crucial for neural stem cell survival. This discovery offers new therapeutic avenues for neurodegenerative diseases by targeting TLX function.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Pharmacology

Background:

  • The orphan nuclear receptor tailless homologue (TLX) is vital for neural stem cell survival and a potential drug target for neurodegeneration.
  • Limited understanding of TLX function hinders therapeutic development due to a lack of identified ligands.

Purpose of the Study:

  • To identify novel modulators of TLX function.
  • To elucidate the mechanism by which TLX activity is regulated.

Main Methods:

  • Screening for TLX modulators using xanthine compounds (caffeine, istradefylline).
  • Site-directed mutagenesis of the TLX ligand-binding domain.
  • Assays for co-repressor recruitment, TLX homodimerization, and heterodimerization with retinoid X receptor.

Main Results:

  • Xanthines were identified as TLX modulators that inhibit its intrinsic repressor activity.
  • Mutagenesis studies suggest direct ligand interaction within the TLX ligand-binding domain (helix 5).
  • Ligand-dependent protein-protein interactions involving co-repressors and dimerization partners (TLX, RXR) were observed.

Conclusions:

  • Xanthines serve as valuable tool compounds for studying TLX.
  • TLX function is modulated by ligand-sensitive protein-protein interactions.
  • TLX plays a novel role in directly repressing other nuclear receptors.

More Related Videos

A Non-random Mouse Model for Pharmacological Reactivation of Mecp2 on the Inactive X Chromosome08:27

A Non-random Mouse Model for Pharmacological Reactivation of Mecp2 on the Inactive X Chromosome

Published on: May 22, 2019

6.5K
Pooled shRNA Screen for Reactivation of MeCP2 on the Inactive X Chromosome11:15

Pooled shRNA Screen for Reactivation of MeCP2 on the Inactive X Chromosome

Published on: March 2, 2018

7.4K

Related Concept Videos

Transducer Mechanism: Nuclear Receptors01:31

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
1.8K
Inheritance of Chromatin Structures03:17

Inheritance of Chromatin Structures

Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...
6.8K
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...
7.7K
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
7.2K
X-Inactivation01:58

X-Inactivation

The human X chromosome contains over ten times the number of genes as in the Y chromosome. Since males have only one X chromosome, and females have two, one might expect females to produce twice as many of the proteins, with undesirable results.
39.8K
Prokaryotic Transcriptional Activators and Repressors01:58

Prokaryotic Transcriptional Activators and Repressors

The organization of prokaryotic genes in their genome is notably different from that of eukaryotes. Prokaryotic genes are organized, such that the genes for proteins involved in the same biochemical process or function are located together in groups. This group of genes, along with their regulatory elements, are collectively known as an operon. The functional genes in an operon are transcribed together to give a single strand of mRNA known as polycistronic mRNA.
Transcription of prokaryotic...
22.5K