ArticleThe Journal of biological chemistry2015
A novel link between Fic (filamentation induced by cAMP)-mediated adenylylation/AMPylation and the unfolded protein response.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed, 123 citations in OpenAlex.
- Article
- Inhibition of FicD-mediated AMPylation and deAMPylation by isoprenoid diphosphates.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Increased FICD-mediated protein AMPylation triggers conserved endoplasmic reticulum stress signaling across species.Cell stress & chaperones · 2026Article
- Recent insights into HSP70: proteostasis and beyond.Frontiers in molecular biosciences · 2026Review
- AMPylation: key roles in biological regulation across prokaryotes and eukaryotes.Frontiers in cellular and infection microbiology · 2026Review
- The rise of AMPylation: from bacterial beginnings to modern implications in health and disease.Biochemical Society transactions · 2025Review
- The functional dynamics of FicD's TPR domain are modulated by the interaction with ATP and BiP.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A repurposed AMP binding domain reveals mitochondrial protein AMPylation as a regulator of cellular metabolism.Nature communications · 2025Article
- 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
- The structural and functional dynamics of BiP and Grp94: opportunities for therapeutic discovery.Trends in pharmacological sciences · 2025Review
- Small-Molecule FICD Inhibitors Suppress Endogenous and Pathologic FICD-Mediated Protein AMPylation.ACS chemical biology · 2025Article
- A statistical mechanics investigation of unfolded protein response across organisms.Scientific reports · 2024Article
- Loss of Fic causes progressive neurodegeneration in a Drosophila model of hereditary spastic paraplegia.Biochimica et biophysica acta. Molecular basis of disease · 2024Article
- FicD sensitizes cellular response to glucose fluctuations in mouse embryonic fibroblasts.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Small molecule FICD inhibitors suppress endogenous and pathologic FICD-mediated protein AMPylation.bioRxiv : the preprint server for biology · 2024Article
- Pronucleotide Probes Reveal a Diverging Specificity for AMPylation vs UMPylation of Human and Bacterial Nucleotide Transferases.Biochemistry · 2024Article
- Article
- Allnighter pseudokinase-mediated feedback links proteostasis and sleep in Drosophila.Nature communications · 2023Article
- Infancy-onset diabetes caused by de-regulated AMPylation of the human endoplasmic reticulum chaperone BiP.EMBO molecular medicine · 2023Article
18 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The maintenance of endoplasmic reticulum (ER) homeostasis is a critical aspect of determining cell fate and requires a properly functioning unfolded protein response (UPR). We have discovered a previously unknown role of a post-translational modification termed adenylylation/AMPylation in regulating signal transduction events during UPR induction. A family of enzymes, defined by the presence of a Fic (filamentation induced by cAMP) domain, catalyzes this adenylylation reaction. The human genome encodes a single Fic protein, called HYPE (Huntingtin yeast interacting protein E), with adenylyltransferase activity but unknown physiological target(s). Here, we demonstrate that HYPE localizes to the lumen of the endoplasmic reticulum via its hydrophobic N terminus and adenylylates the ER molecular chaperone, BiP, at Ser-365 and Thr-366. BiP functions as a sentinel for protein misfolding and maintains ER homeostasis. We found that adenylylation enhances BiP's ATPase activity, which is required for refolding misfolded proteins while coping with ER stress. Accordingly, HYPE expression levels increase upon stress. Furthermore, siRNA-mediated knockdown of HYPE prevents the induction of an unfolded protein response. Thus, we identify HYPE as a new UPR regulator and provide the first functional data for Fic-mediated adenylylation in mammalian signaling.
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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.