Human Keratinocyte Differentiation Requires Translational Control by the eIF2α Kinase GCN2

The Journal of Investigative Dermatology
Ann E CollierDan F Spandau

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 diffe...Continue Reading

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Jan 13, 2018·Frontiers in Immunology·Srikanth BattuNooruddin Khan
Feb 15, 2018·Cold Spring Harbor Perspectives in Biology·Ronald C Wek
Dec 20, 2018·Epigenomics·Katerina GrafanakiConstantinos Stathopoulos
Mar 17, 2019·BMC Genomics·Isabela Tiemy PereiraBruno Dallagiovanna
Feb 12, 2020·Mechanisms of Development·Priya KohliDeborah Eastman
May 7, 2020·Trends in Molecular Medicine·Danay CibrianFrancisco Sánchez-Madrid

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