ArticleMolecular and cellular biology2012
Nerve growth factor-induced cell cycle reentry in newborn neurons is triggered by p38MAPK-dependent E2F4 phosphorylation.
Article in Molecular and cellular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 41 citations in OpenAlex.
- Resistance of E2F4DN to p38Scientific reports · 2026Article
- E2F4DN Transgenic Mice: A Tool for the Evaluation of E2F4 as a Therapeutic Target in Neuropathology and Brain Aging.International journal of molecular sciences · 2022Review
- Article
- p75NTR Promotes Astrocyte Proliferation in Response to Cortical Stab Wound.Cellular and molecular neurobiology · 2022Article
- A Mutant Variant of E2F4 Triggers Multifactorial Therapeutic Effects in 5xFAD Mice.Molecular neurobiology · 2022Article
- Human embryonic genome activation initiates at the one-cell stage.Cell stem cell · 2022Article
- E2F4-Based Gene Therapy Mitigates the Phenotype of the Alzheimer's Disease Mouse Model 5xFAD.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Article
- An overview of mammalian p38 mitogen-activated protein kinases, central regulators of cell stress and receptor signaling.F1000Research · 2020Review
- E2F4 regulates transcriptional activation in mouse embryonic stem cells independently of the RB family.Nature communications · 2019Article
- Neuronal tetraploidy in Alzheimer and aging.Aging · 2017Article
- Aberrant activation of Cdc2/cyclin B1 is involved in initiation of cytoskeletal pathology in murine Niemann-Pick disease type C.Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban · 2017Article
- Strand-specific CpG hemimethylation, a novel epigenetic modification functional for genomic imprinting.Nucleic acids research · 2017Article
- Effects of whole genome duplication on cell size and gene expression in mouse embryonic stem cells.The Journal of reproduction and development · 2016Article
- Novel functions for the transcription factor E2F4 in development and disease.Cell cycle (Georgetown, Tex.) · 2016Review
- Article
- Integrative Genomic Analyses Yield Cell-Cycle Regulatory Programs with Prognostic Value.Molecular cancer research : MCR · 2016Article
- Chromatin-wide and transcriptome profiling integration uncovers p38α MAPK as a global regulator of skeletal muscle differentiation.Skeletal muscle · 2016Article
- Exogenous nerve growth factor protects the hypoglossal nerve against crush injury.Neural regeneration research · 2015Article
- p27(Kip1) participates in the regulation of endoreplication in differentiating chick retinal ganglion cells.Cell cycle (Georgetown, Tex.) · 2015Article
- Neuronal cell cycle: the neuron itself and its circumstances.Cell cycle (Georgetown, Tex.) · 2015Review
Corrections and comments
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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
Cumulative evidence indicates that activation of cyclin D-dependent kinase 4/6 (cdk4/6) represents a major trigger of cell cycle reentry and apoptosis in vertebrate neurons. We show here the existence of another mechanism triggering cell cycle reentry in differentiating chick retinal neurons (DCRNs), based on phosphorylation of E2F4 by p38(MAPK). We demonstrate that the activation of p75(NTR) by nerve growth factor (NGF) induces nuclear p38(MAPK) kinase activity, which leads to Thr phosphorylation and subsequent recruitment of E2F4 to the E2F-responsive cdc2 promoter. Inhibition of p38(MAPK), but not of cdk4/6, specifically prevents NGF-dependent cell cycle reentry and apoptosis in DCRNs. Moreover, a constitutively active form of chick E2F4 (Thr261Glu/Thr263Glu) stimulates G(1)/S transition and apoptosis, even after inhibition of p38(MAPK) activity. In contrast, a dominant-negative E2F4 form (Thr261Ala/Thr263Ala) prevents NGF-induced cell cycle reactivation and cell death in DCRNs. These results indicate that NGF-induced cell cycle reentry in neurons depends on the activation of a novel, cdk4/6-independent pathway that may participate in neurodegeneration.
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