ArticleProceedings of the National Academy of Sciences of the United States of America2017
Unrestrained AMPylation targets cytosolic chaperones and activates the heat shock response.
Article in Proceedings of the National Academy of Sciences of the United States of America, 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, 46 citations in OpenAlex.
- Article
- Profiling of Yeast Saccharomyces cerevisiae Mitochondrial AMPylome Reveals a Regulation of OXPHOS Coupling through ATP Synthase Subunit Delta.Journal of proteome research · 2026Article
- Increased FICD-mediated protein AMPylation triggers conserved endoplasmic reticulum stress signaling across species.Cell stress & chaperones · 2026Article
- FICD (FIC Domain Protein Adenylyl Transferase) Deficiency Protects Mice From Hypertrophy-Induced Heart Failure and Promotes BiP (Binding Immunoglobulin Protein) -Mediated Activation of the Unfolded Protein Response and Endoplasmic Reticulum-Selective Autophagy in Cardiomyocytes.Journal of the American Heart Association · 2025Article
- Loss of FIC-1-mediated AMPylation activates the UPRER and upregulates cytosolic HSP70 chaperones to suppress polyglutamine toxicity.PLoS genetics · 2025Article
- Infancy-onset diabetes caused by de-regulated AMPylation of the human endoplasmic reticulum chaperone BiP.EMBO molecular medicine · 2023Article
- AMPylation and Endoplasmic Reticulum Protein Folding Homeostasis.Cold Spring Harbor perspectives in biology · 2023Review
- Transforming Chemical Proteomics Enrichment into a High-Throughput Method Using an SP2E Workflow.JACS Au · 2022Article
- The AMPylase FIC-1 modulates TGF-β signaling inFrontiers in molecular neuroscience · 2022Article
- Over-expression of the constitutive AMPylase FIC-1(E274G) does not deplete cellular ATP pools inmicroPublication biology · 2021Article
- Fic and non-Fic AMPylases: protein AMPylation in metazoans.Open biology · 2021Article
- Post-translational modifications of Hsp70 family proteins: Expanding the chaperone code.The Journal of biological chemistry · 2020Review
- CryoAPEX - an electron tomography tool for subcellular localization of membrane proteins.Journal of cell science · 2019Article
- Article
- Chaperone AMPylation modulates aggregation and toxicity of neurodegenerative disease-associated polypeptides.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Enzymes Involved in AMPylation and deAMPylation.Chemical reviews · 2018Review
- Fic-mediated deAMPylation is not dependent on homodimerization and rescues toxic AMPylation in flies.The Journal of biological chemistry · 2017Article
- Lower temperatures reduce type I interferon activity and promote alphaviral arthritis.PLoS pathogens · 2017Article
- rAMPing Up Stress Signaling: Protein AMPylation in Metazoans.Trends in cell biology · 2017Review
- Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Protein AMPylation is a conserved posttranslational modification with emerging roles in endoplasmic reticulum homeostasis. However, the range of substrates and cell biological consequences of AMPylation remain poorly defined. We expressed human and Caenorhabditis elegans AMPylation enzymes-huntingtin yeast-interacting protein E (HYPE) and filamentation-induced by cyclic AMP (FIC)-1, respectively-in Saccharomyces cerevisiae, a eukaryote that lacks endogenous protein AMPylation. Expression of HYPE and FIC-1 in yeast induced a strong cytoplasmic Hsf1-mediated heat shock response, accompanied by attenuation of protein translation, massive protein aggregation, growth arrest, and lethality. Overexpression of Ssa2, a cytosolic heat shock protein (Hsp)70, was sufficient to partially rescue growth. In human cell lines, overexpression of active HYPE similarly induced protein aggregation and the HSF1-dependent heat shock response. Excessive AMPylation also abolished HSP70-dependent influenza virus replication. Our findings suggest a mode of Hsp70 inactivation by AMPylation and point toward a role for protein AMPylation in the regulation of cellular protein homeostasis beyond the endoplasmic reticulum.
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Registered trials
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.