ArticleThe Journal of biological chemistry2012
Transforming growth factor-β/SMAD Target gene SKIL is negatively regulated by the transcriptional cofactor complex SNON-SMAD4.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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
33 citing papers in PubMed, 51 citations in OpenAlex.
- ATAD3B and SKIL polymorphisms associated with antipsychotic-induced QTc interval change in patients with schizophrenia: a genome-wide association study.Translational psychiatry · 2022Trial
- A map of intra- and intercellular immune responses across diverse in vitro stimuli and inflammatory disease.Genome medicine · 2026Article
- Mechanotransduction-Induced Gene Expression Reveals Activation of TGFβ/SKIL/TAZ Axis and Supports Invasive Phenotype in Triple-Negative Breast Cancer.International journal of molecular sciences · 2026Article
- Long-term cytokine exposure remodels the methylome and transcriptome of recessive dystrophic epidermolysis bullosa keratinocytes - a bioinformatic analysis.Frontiers in cell and developmental biology · 2026Article
- Pairwise ratio transformation of gene expression data leads to improved checkpoint response prediction in lung cancer patients.BMC bioinformatics · 2025Article
- Donor-dependent regulation of type II and X collagen deposition by early modulation of miR-335-5p and miR-1246 during chondrogenic commitment.Stem cell research & therapy · 2025Article
- Purinergic Receptor P2Y2 Activity Prevents DNA Damage in CClJournal of cellular biochemistry · 2025Article
- Deep phenotyping of patients with MASLD upon high-intensity interval training.JHEP reports : innovation in hepatology · 2025Article
- Differential regulation of Treg stability in human naïve and effector Treg subsets by TGFβ-signaling via ARKADIA-SKI axis.Frontiers in immunology · 2025Article
- Reversible downregulation of MYC in a spheroid model of metastatic epithelial ovarian cancer.Cancer gene therapy · 2025Article
- Cell-specific AHR-driven differential gene expression in the mouse liver cell following acute TCDD exposure.BMC genomics · 2024Article
- Organic phosphate but not inorganic phosphate regulatesiScience · 2024Article
- Upregulation of the canonical signaling pathway of interferon-gamma is associated with glioblastoma progression.Molecular biology reports · 2024Article
- Gene-network based analysis of human placental trophoblast subtypes identifies critical genes as potential targets of therapeutic drugs.Journal of integrative bioinformatics · 2023Article
- TGF-β/SMAD canonical pathway induces the expression of transcriptional cofactor TAZ in liver cancer cells.Heliyon · 2023Article
- Molecular Mechanisms in Genetic Aortopathy-Signaling Pathways and Potential Interventions.International journal of molecular sciences · 2023Review
- Bone Morphogenetic Proteins Shape TFrontiers in immunology · 2022Review
- The Hippo Pathway Effector Transcriptional Co-activator With PDZ-Binding Motif Correlates With Clinical Prognosis and Immune Infiltration in Colorectal Cancer.Frontiers in medicine · 2022Article
- Chemotherapeutic Drug-Regulated Cytokines Might Influence Therapeutic Efficacy in HCC.International journal of molecular sciences · 2021Review
- Actin Cytoskeleton and Regulation of TGFβ Signaling: Exploring Their Links.Biomolecules · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The human SKI-like (SKIL) gene encodes the SMAD transcriptional corepressor SNON that antagonizes TGF-β signaling. SNON protein levels are tightly regulated by the TGF-β pathway: whereas a short stimulation with TGF-β decreases SNON levels by its degradation via the proteasome, longer TGF-β treatment increases SNON levels by inducing SKIL gene expression. Here, we investigated the molecular mechanisms involved in the self-regulation of SKIL gene expression by SNON. Bioinformatics analysis showed that the human SKIL gene proximal promoter contains a TGF-β response element (TRE) bearing four groups of SMAD-binding elements that are also conserved in mouse. Two regions of 408 and 648 bp of the human SKIL gene (∼2.4 kb upstream of the ATG initiation codon) containing the core promoter, transcription start site, and the TRE were cloned for functional analysis. Binding of SMAD and SNON proteins to the TRE region of the SKIL gene promoter after TGF-β treatment was demonstrated by ChIP and sequential ChIP assays. Interestingly, the SNON-SMAD4 complex negatively regulated basal SKIL gene expression through binding the promoter and recruiting histone deacetylases. In response to TGF-β signal, SNON is removed from the SKIL gene promoter, and then the activated SMAD complexes bind the promoter to induce SKIL gene expression. Subsequently, the up-regulated SNON protein in complex with SMAD4 represses its own expression as part of the negative feedback loop regulating the TGF-β pathway. Accordingly, when the SNON-SMAD4 complex is absent as in some cancer cells lacking SMAD4 the regulation of some TGF-β target genes is modified.
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.