ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2011
Gene targeting by the vitamin D response element binding protein reveals a role for vitamin D in osteoblast mTOR signaling.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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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.
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Who cites it
58 citing papers in PubMed, 117 citations in OpenAlex.
- 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 exert distinct effects on human skeletal muscle function and gene expression.PloS one · 2017Trial
- The interplay between childhood obesity and vitamin D deficiency: mechanisms and implications.Frontiers in pediatrics · 2025Review
- Changes in bone density and microarchitecture in adolescents undergoing a first kidney transplantation: a prospective study.European journal of pediatrics · 2024Article
- Vitamin D in tuberous sclerosis complex-associated tumors.Frontiers in pediatrics · 2024Article
- The stress-responsive protein REDD1 and its pathophysiological functions.Experimental & molecular medicine · 2023Review
- The impact of vitamin D on cancer: A mini review.The Journal of steroid biochemistry and molecular biology · 2023Review
- Screening for autophagy/hypoxia/ferroptosis/pyroptosis-related genes of tendon injury and repair in a rat model after celecoxib and lactoferrin treatment.Journal of orthopaedic surgery and research · 2023Article
- Vitamin D inhibits osteosarcoma by reprogramming nonsense-mediated RNA decay and SNAI2-mediated epithelial-to-mesenchymal transition.Frontiers in oncology · 2023Article
- Vitamin D stimulates placental L-type amino acid transporter 1 (LAT1) in preeclampsia.Scientific reports · 2022Article
- Abnormal mTOR Activity in Pediatric Autoimmune Neuropsychiatric and MIA-Associated Autism Spectrum Disorders.International journal of molecular sciences · 2022Review
- Therapeutic effect of acute and chronic use of different doses of vitamin D3 on seizure responses and cognitive impairments induced by pentylenetetrazole in immature male rats.Iranian journal of basic medical sciences · 2022Article
- Vitamin D Modulation of Mitochondrial Oxidative Metabolism and mTOR Enforces Stress Adaptations and Anticancer Responses.JBMR plus · 2022Article
- Causal Links between Hypovitaminosis D and Dysregulation of the T Cell Connection of Immunity Associated with Obesity and Concomitant Pathologies.Biomedicines · 2021Review
- Role of Melatonin in Angiotensin and Aging.Molecules (Basel, Switzerland) · 2021Review
- Is Vitamin D Deficiency Related to Increased Cancer Risk in Patients with Type 2 Diabetes Mellitus?International journal of molecular sciences · 2021Review
- Effects of Vitamin D Supplementation on CD4Nutrients · 2021Article
- Review
- Article
- DEPTOR in Skeletal Development and Diseases.Frontiers in genetics · 2021Review
- Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Transcriptional regulation by hormonal 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] involves occupancy of vitamin D response elements (VDREs) by the VDRE binding protein (VDRE-BP) or 1,25(OH)(2)D(3)-bound vitamin D receptor (VDR). This relationship is disrupted by elevated VDRE-BP, causing a form of hereditary vitamin D-resistant rickets (HVDRR). DNA array analysis showed that of 114 genes regulated by 1,25(OH)(2)D(3) in control cells, almost all (113) were rendered insensitive to the hormone in VDRE-BP-overexpressing HVDRR cells. Among these was the gene for DNA-damage-inducible transcript 4 (DDIT4), an inhibitor of mammalian target of rapamycin (mTOR) signaling. Chromatin immunoprecipitation PCR using 1,25(OH)(2)D(3)-treated osteoblasts confirmed that VDR and VDRE-BP compete for binding to the DDIT4 gene promoter. Expression of DDIT4 mRNA in these cells was induced (1.6-6 fold) by 1,25(OH)(2)D(3) (10-100 nM), and Western blot and flow cytometry analysis showed that this response involved suppression of phosphorylated S6K1(T389) (a downstream target of mTOR) similar to rapamycin treatment. siRNA knockdown of DDIT4 completely abrogated antiproliferative responses to 1,25(OH)(2)D(3), whereas overexpression of VDRE-BP exerted a dominant-negative effect on transcription of 1,25(OH)(2)D(3)-target genes. DDIT4, an inhibitor of mTOR signaling, is a direct target for 1,25(OH)(2)D(3) and VDRE-BP, and functions to suppress cell proliferation in response to vitamin D.
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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.