ArticleThe Journal of biological chemistry2005
Evolutionary trace-based peptides identify a novel asymmetric interaction that mediates oligomerization in nuclear receptors.
Article in The Journal of biological chemistry, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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
15 citing papers in PubMed.
- Mitofusin 2 Mediates the Protective Effect of NR6A1 Silencing Against Neuronal Injury in Experimental Stroke Models.Molecular neurobiology · 2025Article
- International Union of Basic and Clinical Pharmacology CXIII: Nuclear Receptor Superfamily-Update 2023.Pharmacological reviews · 2023Review
- Identification of evolutionarily stable functional and immunogenic sites across the SARS-CoV-2 proteome and greater coronavirus family.Bioinformatics (Oxford, England) · 2021Article
- Identification of evolutionarily stable functional and immunogenic sites across the SARS-CoV-2 proteome and the greater coronavirus family.Research square · 2021Article
- An Evolutionary Trace method defines functionally important bases and sites common to RNA families.PLoS computational biology · 2020Article
- The orphan nuclear receptors at their 25-year reunion.Journal of molecular endocrinology · 2013Review
- Minireview: the diverse roles of nuclear receptors in the regulation of embryonic stem cell pluripotency.Molecular endocrinology (Baltimore, Md.) · 2013Review
- Evolutionary trace for prediction and redesign of protein functional sites.Methods in molecular biology (Clifton, N.J.) · 2012Article
- Differential recruitment of methyl CpG-binding domain factors and DNA methyltransferases by the orphan receptor germ cell nuclear factor initiates the repression and silencing of Oct4.Stem cells (Dayton, Ohio) · 2011Article
- Article
- Orphan nuclear receptors as targets for drug development.Pharmaceutical research · 2010Review
- DNA-dependent oligomerization of herpes simplex virus type 1 regulatory protein ICP4.Journal of virology · 2007Article
- Functional residues serve a dominant role in mediating the cooperativity of the protein ensemble.Proceedings of the National Academy of Sciences of the United States of America · 2007Article
- Nuclear Receptors in Regulation of Mouse ES Cell Pluripotency and Differentiation.PPAR research · 2007Article
- Differential recruitment of methylated CpG binding domains by the orphan receptor GCNF initiates the repression and silencing of Oct4 expression.Molecular and cellular biology · 2006Article
Corrections and comments
- Commented on by
Authors and funding
8 authors.
Funding
Abstract
Germ cell nuclear factor (GCNF) is an orphan nuclear receptor that plays important roles in development and reproduction, by repressing the expression of essential genes such as Oct4, GDF9, and BMP15, through binding to DR0 elements. Surprisingly, whereas recombinant GCNF binds to DR0 sequences as a homodimer, endogenous GCNF does not exist as a homodimer but rather as part of a large complex termed the transiently retinoid-induced factor (TRIF). Here, we use evolutionary trace (ET) analysis to design mutations and peptides that probe the molecular basis for the formation of this unusual complex. We find that GCNF homodimerization and TRIF complex formation are DNA-dependent, and ET suggests that dimerization involves key functional sites on both helix 3 and helix 11, which are located on opposing surfaces of the ligand binding domain. Targeted mutations in either helix of GCNF disrupt the formation of both the homodimer and the endogenous TRIF complex. Moreover, peptide mimetics of both of these ET-determined sites inhibit dimerization and TRIF complex formation. This suggests that a novel helix 3-helix 11 heterotypic interaction mediates GCNF interaction and would facilitate oligomerization. Indeed, it was determined that the endogenous TRIF complex is composed of a GCNF oligomer. These findings shed light on an evolutionarily selected mechanism that reveals the unusual DNA-binding, dimerization, and oligomerization properties of GCNF.
Indexed as
Identifiers
15994320What 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.