ArticleThe Journal of investigative dermatology2017
Human Keratinocyte Differentiation Requires Translational Control by the eIF2α Kinase GCN2.
Article in The Journal of investigative dermatology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- An inhibitor of GCN2 and the integrated stress response directly targets ZAK protein kinase to limit cytotoxicity.The Journal of biological chemistry · 2026Article
- Valorization of Chum Salmon (Marine drugs · 2026Article
- From basic biology to engineered therapies: the keratinocyte stem cell playbook.Frontiers in medical technology · 2026Review
- PERK protein kinase facilitates keratinocyte collective cell migration by engagement with cell adhesion molecules, independent of its kinase activity.Molecular biology of the cell · 2025Article
- Emerging roles for integrated stress response signaling in homeostasis.The FEBS journal · 2025Review
- Inhibition of the Integrated stress response by Epstein-Barr virus oncoprotein LMP1 attenuates epithelial cell differentiation and lytic viral reactivation.PLoS pathogens · 2025Article
- Glucose binds and activates NSUN2 to promote translation and epidermal differentiation.Nucleic acids research · 2024Article
- Skin Lipid Barrier: Structure, Function and Metabolism.Allergy, asthma & immunology research · 2024Review
- Multiple mechanisms activate GCN2 eIF2 kinase in response to diverse stress conditions.Nucleic acids research · 2024Article
- Exploring the Functions of Mutant p53 throughCurrent issues in molecular biology · 2024Article
- Human skin specific long noncoding RNA HOXC13-AS regulates epidermal differentiation by interfering with Golgi-ER retrograde transport.Cell death and differentiation · 2023Article
- Multiple Roles of the Stress Sensor GCN2 in Immune Cells.International journal of molecular sciences · 2023Review
- Article
- Research Techniques Made Simple: Studying Circular RNA in Skin Diseases.The Journal of investigative dermatology · 2021Review
- Novel Insights Into Cellular Changes in HPV8-E7 Positive Keratinocytes: A Transcriptomic and Proteomic Analysis.Frontiers in microbiology · 2021Article
- Cardiomyogenic differentiation is fine-tuned by differential mRNA association with polysomes.BMC genomics · 2019Article
- Translation regulation in skin cancer from a tRNA point of view.Epigenomics · 2019Review
- Role of eIF2α Kinases in Translational Control and Adaptation to Cellular Stress.Cold Spring Harbor perspectives in biology · 2018Review
- Translational control of a humanMolecular biology of the cell · 2018Article
- Translational Control in the Latency of Apicomplexan Parasites.Trends in parasitology · 2017Review
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
Appropriate and sequential differentiation of keratinocytes is essential for all functions of the human epidermis. Although transcriptional regulation has proven to be important for keratinocyte differentiation, little is known about the role of translational control. A key mechanism for modulating translation is through phosphorylation of the α subunit of eukaryotic initiation factor 2 (eIF2). A family of different eIF2α kinases function in the integrative stress response to inhibit general protein synthesis coincident with preferential translation of select mRNAs that participate in stress alleviation. Here we demonstrate that translational control through eIF2α phosphorylation is required for normal keratinocyte differentiation. Analyses of polysome profiles revealed that key differentiation genes, including involucrin, are bound to heavy polysomes during differentiation, despite decreased general protein synthesis. Induced eIF2α phosphorylation by the general control nonderepressible 2 (GCN2) protein kinase facilitated translational control and differentiation-specific protein expression during keratinocyte differentiation. Furthermore, loss of GCN2 thwarted translational control, normal epidermal differentiation, and differentiation gene expression in organotypic skin culture. These findings underscore a previously unknown function for GCN2 phosphorylation of eIF2α and translational control in the formation of an intact human epidermis.
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