ArticleGenes & development2015
Structural basis for corepressor assembly by the orphan nuclear receptor TLX.
Article in Genes & development, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 27 citations in OpenAlex.
- Structural Elucidation and Covalent Modulation of the Autorepressed Orphan Nuclear Receptor NR2F6.ACS chemical biology · 2025Article
- Comparative Evaluation and Profiling of Chemical Tools for the Nuclear Hormone Receptor Family 2.ACS pharmacology & translational science · 2025Article
- A NR2E1-interacting peptide of LSD1 inhibits the proliferation of brain tumour initiating cells.Cell proliferation · 2023Article
- The Transcriptional Repressor Orphan Nuclear Receptor TLX Is Responsive to Xanthines.ACS pharmacology & translational science · 2021Article
- TLX, an Orphan Nuclear Receptor With Emerging Roles in Physiology and Disease.Endocrinology · 2021Review
- Tailless/TLX reverts intermediate neural progenitors to stem cells driving tumourigenesis via repression ofeLife · 2020Article
- Computer-Aided Discovery of Small Molecule Inhibitors of Transcriptional Activity of TLX (NR2E1) Nuclear Receptor.Molecules (Basel, Switzerland) · 2018Article
- Heterodimers of photoreceptor-specific nuclear receptor (PNR/NR2E3) and peroxisome proliferator-activated receptor-γ (PPARγ) are disrupted by retinal disease-associated mutations.Cell death & disease · 2017Article
- TLX-Its Emerging Role for Neurogenesis in Health and Disease.Molecular neurobiology · 2017Review
- Visualizing the Architectures and Interactions of Nuclear Receptors.Endocrinology · 2016Review
- Co-activator candidate interactions for orphan nuclear receptor NR2E1.BMC genomics · 2016Article
- Crystal structures of MBP fusion proteins.Protein science : a publication of the Protein Society · 2016Review
- The Orphan Nuclear Receptor TLX/NR2E1 in Neural Stem Cells and Diseases.Neuroscience bulletin · 2016Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
The orphan nuclear receptor TLX regulates neural stem cell self-renewal in the adult brain and functions primarily as a transcription repressor through recruitment of Atrophin corepressors, which bind to TLX via a conserved peptide motif termed the Atro box. Here we report crystal structures of the human and insect TLX ligand-binding domain in complex with Atro box peptides. In these structures, TLX adopts an autorepressed conformation in which its helix H12 occupies the coactivator-binding groove. Unexpectedly, H12 in this autorepressed conformation forms a novel binding pocket with residues from helix H3 that accommodates a short helix formed by the conserved ALXXLXXY motif of the Atro box. Mutations that weaken the TLX-Atrophin interaction compromise the repressive activity of TLX, demonstrating that this interaction is required for Atrophin to confer repressor activity to TLX. Moreover, the autorepressed conformation is conserved in the repressor class of orphan nuclear receptors, and mutations of corresponding residues in other members of this class of receptors diminish their repressor activities. Together, our results establish the functional conservation of the autorepressed conformation and define a key sequence motif in the Atro box that is essential for TLX-mediated repression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.