ArticleNucleic acids research2013
Prospero-related homeobox 1 (Prox1) functions as a novel modulator of retinoic acid-related orphan receptors α- and γ-mediated transactivation.
Article in Nucleic acids research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 29 citations in OpenAlex.
- CLOCK/BMAL1 interactome uncovers homeodomain factors as tissue regulators.Nature cell biology · 2026Article
- From Nuclear Receptor Regulation to Spleen Activating and Accumulation Resolving Therapy: A Review of Traditional Chinese Medicine Against Diabetes and Inflammation.International journal of molecular sciences · 2025Review
- Molecular and metabolic orchestration of the lymphatic vasculature in physiology and pathology.Nature communications · 2023Review
- International Union of Basic and Clinical Pharmacology CXIII: Nuclear Receptor Superfamily-Update 2023.Pharmacological reviews · 2023Review
- Prox1 Suppresses the Proliferation of Breast Cancer Cells via Direct Inhibition of c-Myc Gene Expression.Cells · 2023Article
- Single-cell analysis of lymphatic endothelial cell fate specification and differentiation during zebrafish development.The EMBO journal · 2023Article
- New High-Throughput Screen Discovers Novel Ligands of Full-Length Nuclear Receptor LRH-1.ACS chemical biology · 2023Article
- Differential gene co-expression network analyses reveal novel molecules associated with transcriptional dysregulation of key biological processes in osteoarthritis knee cartilage.Osteoarthritis and cartilage open · 2022Article
- PROX1 promotes breast cancer invasion and metastasis through WNT/β-catenin pathway via interacting with hnRNPK.International journal of biological sciences · 2022Article
- Prox1 inhibits neurite outgrowth during central nervous system development.Cellular and molecular life sciences : CMLS · 2021Article
- Review
- Ras Pathways on Prox1 and Lymphangiogenesis: Insights for Therapeutics.Frontiers in cardiovascular medicine · 2020Review
- Prox1 represses IL-2 gene expression by interacting with NFAT2.Oncotarget · 2017Article
- An HDAC3-PROX1 corepressor module acts on HNF4α to control hepatic triglycerides.Nature communications · 2017Article
- The Hepatic Lymphatic Vascular System: Structure, Function, Markers, and Lymphangiogenesis.Cellular and molecular gastroenterology and hepatology · 2016Review
- Phenotypically anchored transcriptome profiling of developmental exposure to the antimicrobial agent, triclosan, reveals hepatotoxicity in embryonic zebrafish.Toxicology and applied pharmacology · 2016Article
- DNA methylation regulates hypothalamic gene expression linking parental diet during pregnancy to the offspring's risk of obesity in Psammomys obesus.International journal of obesity (2005) · 2016Article
- Aberrant Activation of Notch Signaling Inhibits PROX1 Activity to Enhance the Malignant Behavior of Thyroid Cancer Cells.Cancer research · 2016Article
- Isoflavones enhance interleukin-17 gene expression via retinoic acid receptor-related orphan receptors α and γ.Toxicology · 2015Article
- The rs340874 PROX1 type 2 diabetes mellitus risk variant is associated with visceral fat accumulation and alterations in postprandial glucose and lipid metabolism.Genes & nutrition · 2015Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
In this study, we identify Prospero-related homeobox 1 (Prox1) as a novel co-repressor of the retinoic acid-related orphan receptors, RORα and RORγ. Prox1 interacts directly with RORγ and RORα and negatively regulates their transcriptional activity. The AF2 domain of RORs is essential for the interaction, whereas Prox1 interacts with RORs through either its 28 amino acids N-terminal region or its C-terminal prospero-like domain. RORγ antagonists stabilize the interaction between RORγ and Prox1. The homeodomain and the interaction through the prospero-like domain of Prox1 are critical for its repression of ROR transcriptional activity. Chromatin immunoprecipitation analysis demonstrated that in liver, Prox1 is recruited to the ROR response element sites of the clock genes, brain and muscle Arnt-like protein 1 (Bmal1), neuronal PAS domain protein 2 (Npas2) and cryptochrome 1 (Cry1), as part of the same complex as RORs. Knockdown of Prox1 by siRNAs in human hepatoma Huh-7 cells increased the expression of RORγ and several ROR-target genes, along with increased histone acetylation at these ROR response element sites. Chromatin immunoprecipitation sequencing analysis suggests that Prox1 is a potential ROR target gene in liver, which is supported by the regulation of the rhythmic expression of Prox1 by RORγ. Our data suggest that Prox1 is part of a feedback loop that negatively regulates the transcriptional control of clock and metabolic networks by RORs.
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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.