ArticleMolecular and cellular biology2002
Novel mechanism of nuclear receptor corepressor interaction dictated by activation function 2 helix determinants.
Article in Molecular and cellular biology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 citing papers in PubMed, 95 citations in OpenAlex.
- A unique insertion/duplication in the VDR gene that truncates the VDR causing hereditary 1,25-dihydroxyvitamin D-resistant rickets without alopecia.Archives of biochemistry and biophysics · 2007Trial
- Stomach at the crossroads: nuclear receptor signaling at the interface between what we are and what we eat.Physiological reviews · 2026Review
- High-throughput affinity measurements of direct interactions between activation domains and co-activators.bioRxiv : the preprint server for biology · 2024Article
- Critical Roles of SRC-3 in the Development and Progression of Breast Cancer, Rendering It a Prospective Clinical Target.Cancers · 2023Review
- RAR-related orphan receptor alpha and the staggerer mice: a fine molecular story.Frontiers in endocrinology · 2023Review
- The stem cell quiescence and niche signaling is disturbed in the hair follicle of the hairpoor mouse, an MUHH model mouse.Stem cell research & therapy · 2022Article
- Hairless regulates heterochromatin maintenance and muscle stem cell function as a histone demethylase antagonist.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Poly(rC) binding protein 2 acts as a negative regulator of IRES-mediated translation of Hr mRNA.Experimental & molecular medicine · 2018Article
- Role of Nuclear Receptors in Central Nervous System Development and Associated Diseases.Journal of experimental neuroscience · 2015Review
- The roles of Jumonji-type oxygenases in human disease.Epigenomics · 2014Review
- Characterization of hairless (Hr) and FGF5 genes provides insights into the molecular basis of hair loss in cetaceans.BMC evolutionary biology · 2013Article
- Small-molecule hormones: molecular mechanisms of action.International journal of endocrinology · 2013Article
- Action of RORs and their ligands in (patho)physiology.Trends in endocrinology and metabolism: TEM · 2012Review
- Hairless plays a role in formation of inner root sheath via regulation of Dlx3 gene.The Journal of biological chemistry · 2012Article
- Molecular evolution of HR, a gene that regulates the postnatal cycle of the hair follicle.Scientific reports · 2011Article
- Gene expression profile of the skin in the 'hairpoor' (HrHp) mice by microarray analysis.BMC genomics · 2010Article
- Disruption of the hedgehog signaling pathway contributes to the hair follicle cycling deficiency in Vdr knockout mice.Journal of cellular physiology · 2010Article
- Hairless expression attenuates apoptosis in a mouse model and the COS cell line; involvement of p53.PloS one · 2010Article
- Analysis of hairless corepressor mutants to characterize molecular cooperation with the vitamin D receptor in promoting the mammalian hair cycle.Journal of cellular biochemistry · 2010Article
- Deconstructing repression: evolving models of co-repressor action.Nature reviews. Genetics · 2010Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transcriptional regulation by nuclear receptors is controlled by the concerted action of coactivator and corepressor proteins. The product of the thyroid hormone-regulated mammalian gene hairless (Hr) was recently shown to function as a thyroid hormone receptor corepressor. Here we report that Hr acts as a potent repressor of transcriptional activation by RORalpha, an orphan nuclear receptor essential for cerebellar development. In contrast to other corepressor-nuclear receptor interactions, Hr binding to RORalpha is mediated by two LXXLL-containing motifs, a mechanism associated with coactivator interaction. Mutagenesis of conserved amino acids in the ligand binding domain indicates that RORalpha activity is ligand-dependent, suggesting that corepressor activity is maintained in the presence of ligand. Despite similar recognition helices shared with coactivators, Hr does not compete for the same molecular determinants at the surface of the RORalpha ligand binding domain, indicating that Hr-mediated repression is not simply through displacement of coactivators. Remarkably, the specificity of Hr corepressor action can be transferred to a retinoic acid receptor by exchanging the activation function 2 (AF-2) helix. Repression of the chimeric receptor is observed in the presence of retinoic acid, demonstrating that in this context, Hr is indeed a ligand-oblivious nuclear receptor corepressor. These results suggest a novel molecular mechanism for corepressor action and demonstrate that the AF-2 helix can play a dynamic role in controlling corepressor as well as coactivator interactions. The interaction of Hr with RORalpha provides direct evidence for the convergence of thyroid hormone and RORalpha-mediated pathways in cerebellar development.
Indexed as
Identifiers
What OpenQuestion holds
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.