ArticleThe Journal of biological chemistry2013
IMPACT is a developmentally regulated protein in neurons that opposes the eukaryotic initiation factor 2α kinase GCN2 in the modulation of neurite outgrowth.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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32 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
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- Investigating the neuronal role of the proteasomal ATPase subunit gene PSMC5 in neurodevelopmental proteasomopathies.Nature communications · 2025Article
- Evidence that Xrn1 is in complex with Gcn1, and is required for full levels of eIF2α phosphorylation.The Biochemical journal · 2024Article
- Emerging Role of GCN1 in Disease and Homeostasis.International journal of molecular sciences · 2024Review
- Is there a localized role for translational quality control?RNA (New York, N.Y.) · 2023Article
- Intrinsically dysregulated cellular stress signaling genes and gene networks in postpartum depression.Molecular psychiatry · 2023Article
- Multiple Roles of the Stress Sensor GCN2 in Immune Cells.International journal of molecular sciences · 2023Review
- Structural neuroimaging phenotypes and associated molecular and genomic underpinnings in autism: a review.Frontiers in neuroscience · 2023Review
- Regulation and outcomes of localized RNA translation.Wiley interdisciplinary reviews. RNA · 2022Review
- Penile Cancer-Derived Cells Molecularly Characterized as Models to Guide Targeted Therapies.Cells · 2021Article
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- PKCγ promotes axonal remodeling in the cortico-spinal tract via GSK3β/β-catenin signaling after traumatic brain injury.Scientific reports · 2019Article
- Dietary sulfur amino acid restriction upregulates DICER to confer beneficial effects.Molecular metabolism · 2019Article
- Translation of upstream open reading frames in a model of neuronal differentiation.BMC genomics · 2019Article
- The GCN2 inhibitor IMPACT contributes to diet-induced obesity and body temperature control.PloS one · 2019Article
- Imprinted and ancient gene: a potential mediator of cancer cell survival during tryptophan deprivation.Cell communication and signaling : CCS · 2018Article
- Time-of-Day Dependent Neuronal Injury After Ischemic Stroke: Implication of Circadian Clock Transcriptional Factor Bmal1 and Survival Kinase AKT.Molecular neurobiology · 2018Article
- Genome-wide DNA methylation analysis reveals that mouse chemical iPSCs have closer epigenetic features to mESCs than OSKM-integrated iPSCs.Cell death & disease · 2018Article
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5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The product of the mouse Imprinted and Ancient gene, IMPACT, is preferentially expressed in neurons. We have previously shown that IMPACT overexpression inhibits the activation of the protein kinase GCN2, which signals amino acid starvation. GCN2 phosphorylates the α-subunit of eukaryotic translation initiation factor 2 (eIF2α), resulting in inhibition of general protein synthesis but increased translation of specific messages, such as ATF4. GCN2 is also involved in the regulation of neuronal functions, controlling synaptic plasticity, memory, and feeding behavior. We show here that IMPACT abundance increases during differentiation of neurons and neuron-like N2a cells, whereas GCN2 displays lowered activation levels. Upon differentiation, IMPACT associates with translating ribosomes, enhances translation initiation, and down-regulates the expression of ATF4. We further show that endogenous IMPACT promotes neurite outgrowth whereas GCN2 is a strong inhibitor of spontaneous neuritogenesis. Together, these results uncover the participation of the GCN2-IMPACT module of translational regulation in a highly controlled step in the development of the nervous system.
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