ArticleMolecular and cellular biology2006
Mediator modulates Gli3-dependent Sonic hedgehog signaling.
Article in Molecular and cellular biology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
What it found
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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
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Who cites it
82 citing papers in PubMed, 121 citations in OpenAlex.
- A Comparative Analysis of the Methylation Status of Non-Coding RNA Promoters in Fibroid and Matched Myometrium.International journal of molecular sciences · 2026Article
- Functional characterization of the MED12 p.Arg1138Trp variant in females: implications for neural development and disease mechanism.Molecular medicine (Cambridge, Mass.) · 2025Article
- The Mediator Complex: A Regulatory Hub for Transcriptional Activity of Nuclear Receptors.Cells · 2025Review
- Mediator complex subunit MED23 dampens antiviral innate immunity by restricting RIG-I expression.PLoS biology · 2025Article
- The Effect of Race/Ethnicity and MED12 Mutation on the Expression of Long Non-Coding RNAs in Uterine Leiomyoma and Myometrium.International journal of molecular sciences · 2024Article
- Natural compounds solasonine and alisol B23-acetate target GLI3 signaling to block oncogenesis in MED12-altered breast cancer.Molecular biology research communications · 2024Article
- Positive correlation between the nuclear expression of GPER and pGLI3 in prostate cancer tissues from patients with different Gleason scores.Frontiers in endocrinology · 2024Article
- Engineered MED12 mutations drive leiomyoma-like transcriptional and metabolic programs by altering the 3D genome compartmentalization.Nature communications · 2023Article
- Differential Expression of MED12-Associated Coding RNA Transcripts in Uterine Leiomyomas.International journal of molecular sciences · 2023Article
- Engineered MED12 mutations drive uterine fibroid-like transcriptional and metabolic programs by altering the 3D genome compartmentalization.Research square · 2023Article
- A Neanderthal/Denisovan GLI3 variant contributes to anatomical variations in mice.Frontiers in cell and developmental biology · 2023Article
- Genetic alterations in MED12 promote castration-resistant prostate cancer through modulation of GLI3 signaling.Molecular biology research communications · 2023Article
- Multiprotein GLI Transcriptional Complexes as Therapeutic Targets in Cancer.Life (Basel, Switzerland) · 2022Review
- The Mediator complex as a master regulator of transcription by RNA polymerase II.Nature reviews. Molecular cell biology · 2022Review
- The Mediator kinase module: an interface between cell signaling and transcription.Trends in biochemical sciences · 2022Review
- The role of mediator subunit 12 in tumorigenesis and cancer therapeutics.Oncology letters · 2022Review
- GLI3 Is Stabilized by SPOP Mutations and Promotes Castration Resistance via Functional Cooperation with Androgen Receptor in Prostate Cancer.Molecular cancer research : MCR · 2022Article
- Transcription Pause and Escape in Neurodevelopmental Disorders.Frontiers in neuroscience · 2022Review
- Long Noncoding RNA MIAT Modulates the Extracellular Matrix Deposition in Leiomyomas by Sponging MiR-29 Family.Endocrinology · 2021Article
- Tryptophan catabolism is dysregulated in leiomyomas.Fertility and sterility · 2021Article
22 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
The physiological and pathological manifestations of Sonic hedgehog (Shh) signaling arise from the specification of unique transcriptional programs dependent upon key nuclear effectors of the Ci/Gli family of transcription factors. However, the underlying mechanism by which Gli proteins regulate target gene transcription in the nucleus remains poorly understood. Here, we identify and characterize a physical and functional interaction between Gli3 and the MED12 subunit within the RNA polymerase II transcriptional Mediator. We show that Gli3 binds to MED12 and intact Mediator both in vitro and in vivo through a Gli3 transactivation domain (MBD; MED12/Mediator-binding domain) whose activity derives from concerted functional interactions with both Mediator and the histone acetyltransferase CBP. Analysis of MBD truncation mutants revealed an excellent correlation between the in vivo activation strength of an MBD derivative and its ability to bind MED12 and intact Mediator in vitro, indicative of a critical functional interaction between the Gli3 MBD and the MED12 interface in Mediator. Disruption of the Gli3-MED12 interaction through dominant-negative interference inhibited, while RNA interference-mediated MED12 depletion enhanced, both MBD transactivation function and Gli3 target gene induction in response to Shh signaling. We propose that activated Gli3 physically targets the MED12 interface within Mediator in order to functionally reverse Mediator-dependent suppression of Shh target gene transcription. These findings thus link MED12 to the modulation of Gli3-dependent Shh signaling and further implicate Mediator in a broad range of developmental and pathological processes driven by Shh signal transduction.
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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.