Increased FICD-mediated protein AMPylation triggers conserved endoplasmic reticulum stress signaling across species.

Mirella A Hernandez-Lima, Blaise L Mariner, William Giblin, Mark A McCormick, Matthias C Truttmann

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Article in Cell stress & chaperones, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 authors.

Mirella A Hernandez-LimaNeuroscience Graduate Program, University of Michigan, Ann Arbor, MI, 48109, USA; Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, 48109, USA.

Blaise L MarinerCenter for Evolution and Medicine, Arizona State University, Tempe, AZ 85287-1701, USA.

William GiblinDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, 48109, USA.

Mark A McCormickSchool of Medicine, University of New Mexico, Albuquerque, NM, USA.

Matthias C TruttmannNeuroscience Graduate Program, University of Michigan, Ann Arbor, MI, 48109, USA; Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, 48109, USA; Geriatrics Center, University of Michigan, Ann Arbor, MI, 48109, USA. Electronic address: mtruttma@med.umich.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Post-translational protein modifications (PTMs) are fundamentally important in regulating protein function across species. One such PTM, referred to as protein AMPylation, is increasingly recognized to fine-tune endoplasmic reticulum (ER) stress signaling in metazoans. Protein AMPylation in the ER is catalyzed by conserved fic-domain containing enzymes (fic AMPylases), including FICD (Homo sapiens) and FIC-1 (Caenorhabditis elegans). However, it remains unclear whether enhanced fic AMPylase-mediated protein AMPylation promotes a conserved cellular response. In this study, we determined the transcriptomic consequences of increased fic AMPylase-mediated protein AMPylation in mouse fibroblasts and young adult nematodes. We find that in C. elegans, FIC-1(E274G) over-expression (OE) triggers a unique transcriptional signature, leading to the marked upregulation of pathways involved in cellular stress signaling. We further show that FIC-1(E274G) OE upregulates genes involved in antibacterial innate immune responses and identify a potentially co-regulated gene cluster sensitive to changes in AMPylation levels. Intriguingly, we observe a similar transcriptomic signature in mouse fibroblasts in response to FICD(E234G) OE. A cross-species comparison of the transcriptomes of nematodes, yeast, and mouse fibroblasts enduring increased fic AMPylase-mediated protein AMPylation revealed a conserved transcriptional core response to enhanced AMPylation. Collectively, this study defines a conserved cellular stress response to enhanced fic AMPylase-mediated protein AMPylation.

Indexed as

Adenosine MonophosphateCaenorhabditis elegans ProteinsEndoplasmic Reticulum StressNucleotidyltransferasesAnimalsCaenorhabditis elegansFibroblastsHumansMembrane ProteinsMiceProtein Processing, Post-TranslationalSignal TransductionAdenosine MonophosphateCaenorhabditis elegans ProteinsFICD protein, humanMembrane ProteinsNucleotidyltransferasesAMPylationBiPER stressFICDUPR

Identifiers

PMID41655743

DOI10.1016/j.cstres.2026.100149

PMCPMC12933456

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