ArticleNucleic acids research2007
The MH1 domain of Smad3 interacts with Pax6 and represses autoregulation of the Pax6 P1 promoter.
Article in Nucleic acids research, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 51 citations in OpenAlex.
- Post-replicative initial expression of PAX6 during neuroectoderm differentiation.The EMBO journal · 2025Article
- The atypical KRASMolecular oncology · 2025Article
- Treatment for type 2 diabetes and diabetic nephropathy by targeting Smad3 signaling.International journal of biological sciences · 2024Article
- Periodontal ligament stem cells as a promising therapeutic target for neural damage.Stem cell research & therapy · 2022Review
- Autoregulation of Pax6 in neuronal cells is mediated by Pax6(5a), Pax6(ΔPD), SPARC, and p53.Molecular biology reports · 2022Article
- Article
- TheDevelopment (Cambridge, England) · 2020Article
- The intracellular domain of CX3CL1 regulates adult neurogenesis and Alzheimer's amyloid pathology.The Journal of experimental medicine · 2019Article
- Investigating the mechanism by which SMAD3 induces PAX6 transcription to promote the development of non-small cell lung cancer.Respiratory research · 2018Article
- SMAD proteins directly suppressOncotarget · 2018Article
- Signaling and Gene Regulatory Networks in Mammalian Lens Development.Trends in genetics : TIG · 2017Review
- Roles of TGFβ and FGF signals during growth and differentiation of mouse lens epithelial cell in vitro.Scientific reports · 2017Article
- Genotype-phenotype correlation of PAX6 gene mutations in aniridia.Human genome variation · 2016Article
- Gene Regulatory Mechanisms Underlying the Spatial and Temporal Regulation of Target-Dependent Gene Expression in Drosophila Neurons.PLoS genetics · 2015Article
- Andrographolide suppresses epithelial mesenchymal transition by inhibition of MAPK signalling pathway in lens epithelial cells.Journal of biosciences · 2015Article
- Transforming growth factor-β1 signaling represses testicular steroidogenesis through cross-talk with orphan nuclear receptor Nur77.PloS one · 2014Article
- Scrib is required for epithelial cell identity and prevents epithelial to mesenchymal transition in the mouse.Developmental biology · 2013Article
- Transforming growth factor β integrates Smad 3 to mechanistic target of rapamycin complexes to arrest deptor abundance for glomerular mesangial cell hypertrophy.The Journal of biological chemistry · 2013Article
- Smad7 protein induces interferon regulatory factor 1-dependent transcriptional activation of caspase 8 to restore tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis.The Journal of biological chemistry · 2013Article
- The expression of Pax6 variants is subject to posttranscriptional regulation in the developing mouse eyelid.PloS one · 2013Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Pax6 transcription is under the control of two main promoters (P0 and P1), and these are autoregulated by Pax6. Additionally, Pax6 expression is under the control of the TGFbeta superfamily, although the precise mechanisms of such regulation are not understood. The effect of TGFbeta on Pax6 expression was studied in the FHL124 lens epithelial cell line and was found to cause up to a 50% reduction in Pax6 mRNA levels within 24 h. Analysis of luciferase reporters showed that Pax6 autoregulation of the P1 promoter, and its induction of a synthetic promoter encoding six paired domain-binding sites, were significantly repressed by both an activated TGFbeta receptor and TGFbeta ligand stimulation. Subsequently, a novel Pax6 binding site in P1 was shown to be necessary for autoregulation, indicating a direct influence of Pax6 protein on P1. In transfected cells, and endogenously in FHL124 cells, Pax6 co-immunoprecipitated with Smad3 following TGFbeta receptor activation, while in GST pull-down experiments, the MH1 domain of Smad3 was observed binding the RED sub-domain of the Pax6 paired domain. Finally, in DNA adsorption assays, activated Smad3 inhibited Pax6 from binding the consensus paired domain recognition sequence. We hypothesize that the Pax6 autoregulatory loop is targeted for repression by the TGFbeta/Smad pathway, and conclude that this involves diminished paired domain DNA-binding function resulting from a ligand-dependant interaction between Pax6 and Smad3.
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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.