ArticleProceedings of the National Academy of Sciences of the United States of America2015
An eIF2α-binding motif in protein phosphatase 1 subunit GADD34 and its viral orthologs is required to promote dephosphorylation of eIF2α.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 88 citations in OpenAlex.
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- Article
- African swine fever virus enhances viral replication by increasing intracellular reduced glutathione levels, which suppresses stress granule formation.Veterinary research · 2024Article
- Protein phosphatase 1 suppresses PKR/EIF2α signaling during human cytomegalovirus infection.Journal of virology · 2024Article
- Mechanism of Decision Making between Autophagy and Apoptosis Induction upon Endoplasmic Reticulum Stress.International journal of molecular sciences · 2024Review
- Substrate recruitment via eIF2γ enhances catalytic efficiency of a holophosphatase that terminates the integrated stress response.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Histone deacetylase inhibitor boosts anticancer potential of fusogenic oncolytic vaccinia virus by enhancing cell-cell fusion.Cancer science · 2024Article
- Recruitment of trimeric eIF2 by phosphatase non-catalytic subunit PPP1R15B.Molecular cell · 2024Article
- Emerging roles of the Protein Phosphatase 1 (PP1) in the context of viral infections.Cell communication and signaling : CCS · 2024Review
- The PPP1R15 Family of eIF2-alpha Phosphatase Targeting Subunits (GADD34 and CReP).International journal of molecular sciences · 2023Review
- WASF3 disrupts mitochondrial respiration and may mediate exercise intolerance in myalgic encephalomyelitis/chronic fatigue syndrome.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- A little less aggregation a little more replication: Viral manipulation of stress granules.Wiley interdisciplinary reviews. RNA · 2023Review
- The integrated stress response in cancer progression: a force for plasticity and resistance.Frontiers in oncology · 2023Review
- Crocodilepox Virus Protein 157 Is an Independently Evolved Inhibitor of Protein Kinase R.Viruses · 2022Article
- ER-phagy in the Occurrence and Development of Cancer.Biomedicines · 2022Review
- Enterovirus 71 Activates GADD34 via Precursor 3CD to Promote IRES-Mediated Viral Translation.Microbiology spectrum · 2022Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Transient protein synthesis inhibition, mediated by phosphorylation of the α subunit of eukaryotic translation initiation factor 2 (eIF2α), is an important protective mechanism cells use during stress conditions. Following relief of the stress, the growth arrest and DNA damage-inducible protein GADD34 associates with the broadly acting serine/threonine protein phosphatase 1 (PP1) to dephosphorylate eIF2α. Whereas the PP1-binding motif on GADD34 has been defined, it remains to be determined how GADD34 directs PP1 to specifically dephosphorylate eIF2α. In this report, we map a novel eIF2α-binding motif to the C terminus of GADD34 in a region distinct from where PP1 binds to GADD34. This motif is characterized by the consensus sequence Rx[Gnl]x(1-2)Wxxx[Arlv]x[Dn][Rg]xRFxx[Rlvk][Ivc], where capital letters are preferred and x is any residue. Point mutations altering the eIF2α-binding motif impair the ability of GADD34 to interact with eIF2α, promote eIF2α dephosphorylation, and suppress PKR toxicity in yeast. Interestingly, this eIF2α-docking motif is conserved among viral orthologs of GADD34, and is necessary for the proteins produced by African swine fever virus, Canarypox virus, and Herpes simplex virus to promote eIF2α dephosphorylation. Taken together, these data indicate that GADD34 and its viral orthologs direct specific dephosphorylation of eIF2α by interacting with both PP1 and eIF2α through independent binding motifs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.