ArticleThe Journal of clinical investigation2011
Gadd45β is an inducible coactivator of transcription that facilitates rapid liver growth in mice.
Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- Contradictory Role of Gadd45β in Liver Diseases.Journal of cellular and molecular medicine · 2024Pooled it
- Hepatic Glucocorticoid Receptor Action and Glucose Homeostasis.Endocrine reviews · 2026Review
- CAR: Discovery and development by the pharmacogenetics laboratory at NIEHS, NIH.Pharmacological research · 2025Review
- CAR requires Gadd45β to promote phenobarbital-induced mouse liver tumors in early stage.Frontiers in oncology · 2023Article
- Clinical Relevance of the Constitutive Androstane Receptor.Drug metabolism and disposition: the biological fate of chemicals · 2022Review
- Lymphocyte-Specific Protein-1 Suppresses Xenobiotic-Induced Constitutive Androstane Receptor and Subsequent Yes-Associated Protein-Activated Hepatocyte Proliferation.The American journal of pathology · 2022Article
- Gadd45 in the Liver: Signal Transduction and Transcriptional Mechanisms.Advances in experimental medicine and biology · 2022Article
- Gadd45 in DNA Demethylation and DNA Repair.Advances in experimental medicine and biology · 2022Article
- The xenobiotic receptors PXR and CAR in liver physiology, an update.Biochimica et biophysica acta. Molecular basis of disease · 2021Review
- Yes-Associated Protein Is Crucial for Constitutive Androstane Receptor-Driven Hepatocyte Proliferation But Not for Induction of Drug Metabolism Genes in Mice.Hepatology (Baltimore, Md.) · 2021Article
- Regulation of dopamine-dependent transcription and cocaine action by Gadd45b.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021Article
- Article
- Noncanonical Constitutive Androstane Receptor Signaling in Gene Regulation.International journal of molecular sciences · 2020Review
- Ablation of Gadd45β ameliorates the inflammation and renal fibrosis caused by unilateral ureteral obstruction.Journal of cellular and molecular medicine · 2020Article
- TCPOBOP-Induced Hepatomegaly and Hepatocyte Proliferation are Attenuated by Combined Disruption of MET and EGFR Signaling.Hepatology (Baltimore, Md.) · 2019Article
- Constitutive Activation of the Human Aryl Hydrocarbon Receptor in Mice Promotes Hepatocarcinogenesis Independent of Its Coactivator Gadd45b.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
- Article
- Overexpression of CYB5R3 and NQO1, two NADAging cell · 2018Article
- Nuclear receptors and liver disease: Summary of the 2017 basic research symposium.Hepatology communications · 2018Review
- Post-hepatectomy liver regeneration in the context of bile acid homeostasis and the gut-liver signaling axis.Journal of clinical and translational research · 2018Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The growth arrest and DNA damage-inducible 45 (Gadd45) proteins act in many cellular processes. In the liver, Gadd45b (encoding Gadd45β) is the gene most strongly induced early during both compensatory regeneration and drug-induced hyperplasia. The latter response is associated with the dramatic and rapid hepatocyte growth that follows administration of the xenobiotic TCPOBOP (1,4-bis[2-(3,5)-dichoropyridyloxy] benzene), a ligand of the nuclear receptor constitutive androstane receptor (CAR). Here, we have shown that Gadd45b-/- mice have intact proliferative responses following administration of a single dose of TCPOBOP, but marked growth delays. Moreover, early transcriptional stimulation of CAR target genes was weaker in Gadd45b-/- mice than in wild-type animals, and more genes were downregulated. Gadd45β was then found to have a direct role in transcription by physically binding to CAR, and TCPOBOP treatment caused both proteins to localize to a regulatory element for the CAR target gene cytochrome P450 2b10 (Cyp2b10). Further analysis defined separate Gadd45β domains that mediated binding to CAR and transcriptional activation. Although baseline hepatic expression of Gadd45b was broadly comparable to that of other coactivators, its 140-fold stimulation by TCPOBOP was striking and unique. The induction of Gadd45β is therefore a response that facilitates increased transcription, allowing rapid expansion of liver mass for protection against xenobiotic insults.
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