ArticleThe Journal of biological chemistry2011
Pregnane X receptor PXR activates the GADD45beta gene, eliciting the p38 MAPK signal and cell migration.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.
- Contradictory Role of Gadd45β in Liver Diseases.Journal of cellular and molecular medicine · 2024Pooled it
- Drug-induced cis-regulatory elements in human hepatocytes affect molecular phenotypes associated with adverse reactions.Nature communications · 2025Article
- Perfluoroalkyl and polyfluoroalkyl substances and Cancer risk: results from a dose-response Meta-analysis.Journal of environmental health science & engineering · 2024Article
- The Transcriptome of BT-20 Breast Cancer Cells Exposed to Curcumin Analog NC2603 Reveals a Relationship between EGR3 Gene Modulation and Cell Migration Inhibition.Molecules (Basel, Switzerland) · 2024Article
- The Pregnane-X receptor regulates steroid synthesis in mouse Leydig cells.Frontiers in endocrinology · 2024Article
- Advances in drug resistance of triple negative breast cancer caused by pregnane X receptor.World journal of clinical oncology · 2023Review
- Gadd45 in the Liver: Signal Transduction and Transcriptional Mechanisms.Advances in experimental medicine and biology · 2022Article
- GADD45 in Stress Signaling, Cell Cycle Control, and Apoptosis.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
- Probiotics mixture reinforces barrier function to ameliorate necrotizing enterocolitis by regulating PXR-JNK pathway.Cell & bioscience · 2021Article
- Review
- Indirubin-pregnane X receptor-JNK axis accelerates skin wound healing.Scientific reports · 2019Article
- A phosphorylation-deficient mutant of retinoid X receptor α at Thr 167 alters fasting response and energy metabolism in mice.Laboratory investigation; a journal of technical methods and pathology · 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
- Pregnane X Receptor Regulates Liver Size and Liver Cell Fate by Yes-Associated Protein Activation in Mice.Hepatology (Baltimore, Md.) · 2019Article
- Overexpression of CYB5R3 and NQO1, two NADAging cell · 2018Article
- Role of c-Jun-N-Terminal Kinase in Pregnane X Receptor-Mediated Induction of Human Cytochrome P4503A4 In Vitro.Drug metabolism and disposition: the biological fate of chemicals · 2018Article
- Gadd45β silencing impaired viability and metastatic phenotypes in cholangiocarcinoma cells by modulating the EMT pathway.Oncology letters · 2018Article
- PXR: More Than Just a Master Xenobiotic Receptor.Molecular pharmacology · 2018Review
- Effects of Lidocaine-Mediated CPEB3 Upregulation in Human Hepatocellular Carcinoma Cell Proliferation In Vitro.BioMed research international · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Pregnane X receptor (PXR) was originally characterized as a transcription factor that induces hepatic drug metabolism by activating cytochrome P450 genes. Here we have now demonstrated a novel function of PXR, that of eliciting p38 mitogen-activated protein kinase (MAPK) phosphorylation for cell migration. Upon xenobiotic activation of ectopic human PXR, human hepatocellular carcinoma HepG2 cells were found to exhibit increased phosphorylation of p38 MAPK and to subsequently change morphology and migrate. p38 MAPK was responsible for the regulation of these morphological changes and cell migration because the p38 MAPK inhibitor SB239063 repressed both. Prior to this phosphorylation, PXR directly activated the early response GADD45β gene by binding to a distal direct repeat 4 site of the GADD45β promoter. Ectopic expression of GADD45β increased p38 MAPK phosphorylation, whereas siRNA knockdown of GADD45β decreased the PXR-induced p38 MAPK phosphorylation, confirming that GADD45β can regulate PXR-induced p38 MAPK phosphorylation in HepG2 cells. These results indicate that PXR activates the GADD45β gene, increasing p38 MAPK phosphorylation, and leading HepG2 cells to change morphology and migrate. The GADD45β gene is a direct target for PXR, eliciting cell signals to regulate various cellular functions.
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.