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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Two distinct nodes of translational inhibition in the Integrated Stress Response

  • Ryoo, Hyung Don (Department of Cell Biology, New York University School of Medicine) ;
  • Vasudevan, Deepika (Department of Cell Biology, New York University School of Medicine)
  • Received : 2017.08.12
  • Published : 2017.11.30
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Abstract

The Integrated Stress Response (ISR) refers to a signaling pathway initiated by stress-activated $eIF2{\alpha}$ kinases. Once activated, the pathway causes attenuation of global mRNA translation while also paradoxically inducing stress response gene expression. A detailed analysis of this pathway has helped us better understand how stressed cells coordinate gene expression at translational and transcriptional levels. The translational attenuation associated with this pathway has been largely attributed to the phosphorylation of the translational initiation factor $eIF2{\alpha}$. However, independent studies are now pointing to a second translational regulation step involving a downstream ISR target, 4E-BP, in the inhibition of eIF4E and specifically cap-dependent translation. The activation of 4E-BP is consistent with previous reports implicating the roles of 4E-BP resistant, Internal Ribosome Entry Site (IRES) dependent translation in ISR active cells. In this review, we provide an overview of the translation inhibition mechanisms engaged by the ISR and how they impact the translation of stress response genes.

Keywords

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