ArticleMolecular and cellular biology2015
The control operated by the cell cycle machinery on MEF2 stability contributes to the downregulation of CDKN1A and entry into S phase.
Article in Molecular and cellular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 56 citations in OpenAlex.
- DYRK1A and Parkinson's disease, facts and hypotheses.Neurobiology of disease · 2026Review
- Fortilin binds and stabilizes MEF2C, activates it through phosphorylation, and drives transcription of the cell structural and survival protein CTNNA3.The Journal of biological chemistry · 2026Article
- HDAC4 influences the DNA damage response and counteracts senescence by assembling with HDAC1/HDAC2 to control H2BK120 acetylation and homology-directed repair.Nucleic acids research · 2024Article
- Single-cell ATAC sequencing identifies sleepy macrophages during reciprocity of cytokines inMicrobiology spectrum · 2024Article
- SKP2 Knockout in Rb1/p53-Deficient Mouse Models of Osteosarcoma Induces Immune Infiltration and Drives a Transcriptional Program with a Favorable Prognosis.Molecular cancer therapeutics · 2024Article
- A Ubiquitin-Dependent Switch on MEF2D Senses Pro-Metastatic Niche Signals to Facilitate Intrahepatic Metastasis of Liver Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Long non-coding RNA generated from CDKN1A gene by alternative polyadenylation regulates p21 expression during DNA damage response.Nucleic acids research · 2023Article
- Synergistic anti-cancer effect of sodium pentaborate pentahydrate, curcumin and piperine on hepatocellular carcinoma cells.Scientific reports · 2023Article
- Phosphorylation of the Myogenic Factor Myocyte Enhancer Factor-2 Impacts Myogenesis In Vivo.Molecular and cellular biology · 2023Article
- Small RNA sequencing identified miR-3180 as a potential prognostic biomarker for Chinese hepatocellular carcinoma patients.Frontiers in genetics · 2023Article
- Regulation of human T-cell leukemia virus type 1 antisense promoter by myocyte enhancer factor-2C in the context of adult T-cell leukemia and lymphoma.Haematologica · 2022Article
- Transcriptomic and genomic studies classify NKL54 as a histone deacetylase inhibitor with indirect influence on MEF2-dependent transcription.Nucleic acids research · 2022Article
- HDAC4 degradation during senescence unleashes an epigenetic program driven by AP-1/p300 at selected enhancers and super-enhancers.Genome biology · 2021Article
- Review
- A Biological Circuit Involving Mef2c, Mef2d, and Hdac9 Controls the Immunosuppressive Functions of CD4+Foxp3+ T-Regulatory Cells.Frontiers in immunology · 2021Article
- MEF2D sustains activation of effector Foxp3+ Tregs during transplant survival and anticancer immunity.The Journal of clinical investigation · 2020Article
- "Amyloid-beta accumulation cycle" as a prevention and/or therapy target for Alzheimer's disease.Aging cell · 2020Review
- Dysregulated mitogen-activated protein kinase pathway mediated cell cycle disruption in sporadic parathyroid tumors.Journal of endocrinological investigation · 2020Article
- MEF2C repressor variant deregulation leads to cell cycle re-entry and development of heart failure.EBioMedicine · 2020Article
- Genetic Programs Driving Oncogenic Transformation: Lessons from in Vitro Models.International journal of molecular sciences · 2019Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
MEF2s are pleiotropic transcription factors (TFs) which supervise multiple cellular activities. During the cell cycle, MEF2s are activated at the G0/G1 transition to orchestrate the expression of the immediate early genes in response to growth factor stimulation. Here we show that, in human and murine fibroblasts, MEF2 activities are downregulated during late G1. MEF2C and MEF2D interact with the E3 ligase F-box protein SKP2, which mediates their subsequent degradation through the ubiquitin-proteasome system. The cyclin-dependent kinase 4 (CDK4)/cyclin D1 complex phosphorylates MEF2D on serine residues 98 and 110, and phosphorylation of these residues is an important determinant for SKP2 binding. Unscheduled MEF2 transcription during the cell cycle reduces cell proliferation, whereas its containment sustains DNA replication. The CDK inhibitor p21/CDKN1A gene is a MEF2 target gene required to exert this antiproliferative influence. MEF2C and MEF2D bind a region within the first intron of CDKN1A, presenting epigenetic markers of open chromatin. Importantly, H3K27 acetylation within this regulative region depends on the presence of MEF2D. We propose that following the initial engagement in the G0/G1 transition, MEF2C and MEF2D must be polyubiquitylated and degraded during G1 progression to diminish the transcription of the CDKN1A gene, thus favoring entry into S phase.
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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.