ArticleCell research2011
HDAC2 phosphorylation-dependent Klf5 deacetylation and RARα acetylation induced by RAR agonist switch the transcription regulatory programs of p21 in VSMCs.
Article in Cell research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It carries an expression of concern. Cited by 38 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
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.
- Silencing of OIP5-AS1 Protects Endothelial Cells From ox-LDL-Triggered Injury by Regulating KLF5 Expression via Sponging miR-135a-5p.Frontiers in cardiovascular medicine · 2021Pooled it
- Increased ATCell death & disease · 2020Trial
- Single-Cell Sequencing Reveals the Crosstalk Between MuSCs and FAPs in Ruminant Skeletal Muscle Development.Cells · 2026Article
- What role do miRNAs play in the injured heart of the infertile female?Biochemistry and biophysics reports · 2025Review
- HDACs and Their Inhibitors on Post-Translational Modifications: The Regulation of Cardiovascular Disease.Cells · 2025Review
- Role of histone post-translational modifications in atherosclerosis and the therapeutic potential of targeting epigenetic modifiers.Frontiers in cell and developmental biology · 2025Review
- Unbiased screening identifies regulators of cell-cell adhesion and treatment options in pemphigus.Nature communications · 2024Article
- Jian Gan powder ameliorates immunological liver injury in mice by modulating the gut microbiota and metabolic profiles.European journal of medical research · 2024Article
- DNA methylation and histone post-translational modifications in atherosclerosis and a novel perspective for epigenetic therapy.Cell communication and signaling : CCS · 2023Review
- Targeting protein modifications in metabolic diseases: molecular mechanisms and targeted therapies.Signal transduction and targeted therapy · 2023Review
- Transcription factors: key regulatory targets of vascular smooth muscle cell in atherosclerosis.Molecular medicine (Cambridge, Mass.) · 2023Review
- The phosphorylation to acetylation/methylation cascade in transcriptional regulation: how kinases regulate transcriptional activities of DNA/histone-modifying enzymes.Cell & bioscience · 2022Review
- Krüppel-like factor (KLF)5: An emerging foe of cardiovascular health.Journal of molecular and cellular cardiology · 2022Review
- Short communication: TNF-α and IGF-1 regulates epigenetic mechanisms of HDAC2 and HDAC10.PloS one · 2022Article
- LINC01123 promotes cell proliferation and migration via regulating miR-1277-5p/KLF5 axis in ox-LDL-induced vascular smooth muscle cells.Journal of molecular histology · 2021Article
- The roles and regulation of the KLF5 transcription factor in cancers.Cancer science · 2021Review
- Current knowledge of Krüppel-like factor 5 and vascular remodeling: providing insights for therapeutic strategies.Journal of molecular cell biology · 2021Review
- Acetylation of KLF5 maintains EMT and tumorigenicity to cause chemoresistant bone metastasis in prostate cancer.Nature communications · 2021Article
- Klf5 down-regulation induces vascular senescence through eIF5a depletion and mitochondrial fission.PLoS biology · 2020Article
- Long non-coding RNA ARAP1-AS1 accelerates cell proliferation and migration in breast cancer through miR-2110/HDAC2/PLIN1 axis.Bioscience reports · 2020Article
Corrections and comments
- Expression of concern
Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Abnormal proliferation of vascular smooth muscle cells (VSMCs) occurs in hypertension, atherosclerosis and restenosis after angioplasty, leading to pathophysiological vascular remodeling. As an important growth arrest gene, p21 plays critical roles in vascular remodeling. Regulation of p21 expression by retinoic acid receptor (RAR) and its ligand has important implications for control of pathological vascular remodeling. Nevertheless, the mechanism of RAR-mediated p21 expression in VSMCs remains poorly understood. Here, we show that, under basal conditions, RARα forms a complex with histone deacetylase 2 (HDAC2) and Krüppel-like factor 5 (Klf5) at the p21 promoter to inhibit its expression. Upon RARα agonist stimulation, HDAC2 is phosphorylated by CK2α. Phosphorylation of HDAC2, on the one hand, promotes its dissociation from RARα, thus allowing the liganded-RARα to interact with co-activators; on the other hand, it increases its interaction with Klf5, thus leading to deacetylation of Klf5. Deacetylation of Klf5 facilitates its dissociation from the p21 promoter, relieving its repressive effect on the p21 promoter. Interference with HDAC2 phosphorylation by either CK2α knockdown or the use of phosphorylation-deficient mutant of HDAC2 prevents the dissociation of Klf5 from the p21 promoter and impairs RAR agonist-induced p21 activation. Our results reveal a novel mechanism involving a phosphorylation-deacetylation cascade that functions to remove the basal repression complex from the p21 promoter upon RAR agonist treatment, allowing for optimum agonist-induced p21 expression.
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.