Regulation and function of elF2B in neurological and metabolic disorders.

HANSON, Filipe, HODGSON, Rachel E, RIBEIRO DE OLIVEIRA, Madalena I, ALLEN, Elizabeth and CAMPBELL, Susan (2022). Regulation and function of elF2B in neurological and metabolic disorders. Bioscience Reports, 42 (6): BSR2021169.

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Abstract

Eukaryotic initiation factor 2B, eIF2B is a guanine nucleotide exchange, factor with a central role in coordinating the initiation of translation.  During stress and disease, the activity of eIF2B is inhibited via the phosphorylation of its substrate eIF2 (p-eIF2α).  A number of different kinases respond to various stresses leading to the phosphorylation of the alpha subunit of eIF2 and collectively this regulation is known as the Integrated Stress Response, ISR.  This targeting of eIF2B allows the cell to regulate protein synthesis and reprogramme gene expression to restore homeostasis. Advances within structural biology have furthered our understanding of how eIF2B interacts with eIF2 in both the productive GEF active form and the non-productive eIF2ɑ phosphorylated form. Here, current knowledge of the role of eIF2B in the ISR is discussed within the context of normal and disease states focussing particularly on diseases such as Vanishing White Matter Disease (VWMD) and Permanent Neonatal Diabetes Mellitus (PNDM), which are directly linked to mutations in eIF2B.  The role of eIF2B in synaptic plasticity and memory formation is also discussed. In addition, the cellular localisation of eIF2B is reviewed and considered along with the role of additional in vivo eIF2B binding factors and protein modifications that may play a role in modulating eIF2B activity during health and disease.

Item Type:	Article
Uncontrolled Keywords:	Protein synthesis; Translational Control; cellular targeting; eukaryotic gene expression; stress response; Biochemistry & Molecular Biology; 0601 Biochemistry and Cell Biology
Identification Number:	https://doi.org/10.1042/BSR20211699
SWORD Depositor:	Symplectic Elements
Depositing User:	Symplectic Elements
Date Deposited:	30 Jun 2022 11:12
Last Modified:	12 Oct 2023 11:16
URI:	https://shura.shu.ac.uk/id/eprint/30391

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