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XPD Mutations Prevent TFIIH-Dependent Transactivation by Nuclear Receptors and Phosphorylation of RARα
Open accessAbstract
Inherited mutations in the XPD subunit of the general transcription/repair factor TFIIH yield the rare genetic disorder Xeroderma pigmentosum (XP), the phenotypes of which cannot be explained solely on the basis of a DNA repair defect. In cells derived from XP-D patients, we observed a reduction of the ligand-dependent transactivation mediated by several nuclear receptors (RARalpha, ERalpha, and AR). We demonstrate that the XPD mutation alters cdk7 function in RARalpha phosphorylation. Transactivation is restored upon overexpression of either the wild-type XPD or the RARalphaS77E (a mutation which mimics phosphorylated RARalpha). Thus, we demonstrate that the cdk7 kinase of TFIIH phosphorylates the nuclear receptor, then allowing ligand-dependent control of the activation of the hormone-responsive genes.
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“In line with this hypothesis, in xeroderma pigmentosum patients, who are characterized by mutations affecting subunits of the core of the general transcription factor TFIIH, RAR ␣ is not effi ciently phosphorylated by cdk7, with characteristic downstream consequences on the expression of RAR target genes ( 162 ).”
From Vitamin A and retinoid signaling: genomic and nongenomic effects (2013) · cites this paper as [162]
In the citing paper
“This defi cient phosphorylation has been correlated at least in part to the clinical abnormalities of the patients.”
From Vitamin A and retinoid signaling: genomic and nongenomic effects (2013) · cites this paper as [162]
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Metadata
- Authors
- Keriel, A., Stary, A., Sarasin, A., Rochette-Egly, C., & Egly, J.-M.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Egly, Jean-Marc
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2002-04
- Volume
- 109
- Issue
- 1
- Pages
- 125-135
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2030054148
- Cited by
- 192
- References
- 59
- Citations by year
- 2025: 3 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 4 · 2020: 5 · 2019: 3 · 2018: 5 · 2017: 3 · 2016: 5 · 2015: 7 · 2014: 12 · 2013: 9 · 2012: 8
- FWCI
- 5.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- XPD, TFIIH, xeroderma pigmentosum, nuclear receptors, RARα, CDK7, ligand-dependent transactivation, estrogen receptor alpha, androgen receptor, transcriptional regulation, DNA repair
- MeSH terms
- Retinoic Acid Receptor alpha, Cyclin-Dependent Kinase-Activating Kinase, Animals, Cell Nucleus, DNA Helicases, DNA-Binding Proteins, Fibroblasts, Gene Expression Regulation, HeLa Cells, Humans, Mutation, Phosphorylation, Proteins, Transcription Factors, Transcription, Genetic, Xeroderma Pigmentosum, Signal Transduction, Transcriptional Activation, Protein Serine-Threonine Kinases, Receptors, Cytoplasmic and Nuclear, Receptors, Retinoic Acid, Cyclin-Dependent Kinases, Transcription Factors, TFII, Transcription Factor TFIIH, Xeroderma Pigmentosum Group D Protein
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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