ArticleThe Journal of biological chemistry2009
Silencing of the transforming growth factor-beta (TGFbeta) receptor II by Kruppel-like factor 14 underscores the importance of a negative feedback mechanism in TGFbeta signaling.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 93 citations in OpenAlex.
- Pooled it
- The KLF14 Variant is Associated with Type 2 Diabetes and HbABiochemical genetics · 2021Trial
- Modulating mesenchymal stromal cells chondrogenesis through TGF-β1 pre-conditioning during monolayer expansion in pellet culture and in a 3D mechanical load model.Journal of translational medicine · 2026Article
- Enhancer of Zeste Homolog 2 Protects Mucosal Melanoma from Ferroptosis via the KLF14-SLC7A11 Signaling Pathway.Cancers · 2024Article
- Disease related changes in ATAC-seq of iPSC-derived motor neuron lines from ALS patients and controls.Nature communications · 2024Article
- KLF transcription factors in bone diseases.Journal of cellular and molecular medicine · 2024Review
- Krüpple-like factors in cardiomyopathy: emerging player and therapeutic opportunities.Frontiers in cardiovascular medicine · 2024Review
- Downregulation of Krüppel-like factor 14 accelerated cellular senescence and aging.Aging cell · 2023Article
- KLF14 regulates the growth of hepatocellular carcinoma cells via its modulation of iron homeostasis through the repression of iron-responsive element-binding protein 2.Journal of experimental & clinical cancer research : CR · 2023Article
- Genome-wide analysis of cis-regulatory changes underlying metabolic adaptation of cavefish.Nature genetics · 2022Article
- Protective function of interleukin-22 in pulmonary fibrosis.Clinical and translational medicine · 2021Article
- EZH2-mediated inhibition of KLF14 expression promotes HSCs activation and liver fibrosis by downregulating PPARγ.Cell proliferation · 2021Article
- Article
- Transcription Factor KLF14 and Metabolic Syndrome.Frontiers in cardiovascular medicine · 2020Review
- Article
- Krϋppel-like factors (KLFs) in renal physiology and disease.EBioMedicine · 2019Review
- Hypertension genomics and cardiovascular prevention.Annals of translational medicine · 2018Review
- Functional validation reveals the novel missense V419L variant inCold Spring Harbor molecular case studies · 2017Article
- Krüppel-like factors in mammalian stem cells and development.Development (Cambridge, England) · 2017Review
- The promise of epigenomic therapeutics in pancreatic cancer.Epigenomics · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The role of non-Smad proteins in the regulation of transforming growth factor-beta (TGFbeta) signaling is an emerging line of active investigation. Here, we characterize the role of KLF14, as a TGFbeta-inducible, non-Smad protein that silences the TGFbeta receptor II (TGFbetaRII) promoter. Together with endocytosis, transcriptional silencing is a critical mechanism for down-regulating TGFbeta receptors at the cell surface. However, the mechanisms underlying transcriptional repression of these receptors remain poorly understood. KLF14 has been chosen from a comprehensive screen of 24 members of the Sp/KLF family due to its TGFbeta inducibility, its ability to regulate the TGFbetaRII promoter, and the fact that this protein had yet to be functionally characterized. We find that KLF14 represses the TGFbetaRII, a function that is augmented by TGFbeta treatment. Mapping of the TGFbetaRII promoter, in combination with site-directed mutagenesis, electromobility shift, and chromatin immunoprecipitation assays, have identified distinct GC-rich sequences used by KLF14 to regulate this promoter. Mechanistically, KLF14 represses the TGFbetaRII promoter via a co-repressor complex containing mSin3A and HDAC2. Furthermore, the TGFbeta pathway activation leads to recruitment of a KLF14-mSin3A-HDAC2 repressor complex to the TGFbetaRII promoter, as well as the remodeling of chromatin to increase histone marks that associate with transcriptional silencing. Thus, these results describe a novel negative-feedback mechanism by which TGFbetaRII activation at the cell surface induces the expression of KLF14 to ultimately silence the TGFbetaRII and further expand the network of non-Smad transcription factors that participate in the TGFbeta pathway.
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.