ArticleNature chemical biology2024
Extensive protein pyrophosphorylation revealed in human cell lines.
Article in Nature chemical biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 35 citations in OpenAlex.
- AMPK phosphorylation proceeds through hierarchical proteoform cascades revealed by integrated mass spectrometry.Science advances · 2026Article
- Protein pyrophosphorylation by inositol pyrophosphates - detection, function, and regulation.FEBS letters · 2026Review
- Inositol pyrophosphate kinases in health and disease.FEBS letters · 2026Review
- Review
- Proteome-wide quantification of inositol pyrophosphate-protein interactions.Nature communications · 2026Article
- Epigenetic regulation and posttranslational modifications of FXR: underlying mechanisms and implications in digestive diseases.Acta pharmacologica Sinica · 2026Review
- Treacle-dependent TOPBP1 condensation regulates the nucleolar DNA damage response.Nucleic acids research · 2026Article
- The inositol pyrophosphate 5-InsPThe Journal of biological chemistry · 2026Article
- Post-Translational Modifications in Animal Circadian Clocks.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Oncometabolite 5-IPNature chemical biology · 2026Article
- Analytical applications of gas-phase ion chemistry enabled by mass spectrometry.Analytical methods : advancing methods and applications · 2026Review
- Energy-Rich Molecules and Group Transfer Potentials in Energetic Coupling Reactions.Molecules (Basel, Switzerland) · 2026Review
- Article
- Nucleoside diphosphate kinase A (NME1) catalyses its own oligophosphorylation.Nature chemistry · 2025Article
- Are you having a LaPh? Diverse roles of Labile Phosphorylation in mammalian cells.Biochemical Society transactions · 2025Review
- Diverse oncogenes use common mechanisms to drive growth of major forms of human cancer.Science advances · 2025Article
- A pH-Centric Model of Nucleolar Activity and Regulation.Journal of molecular biology · 2025Review
- Ubiquitin is directly linked via an ester to protein-conjugated mono-ADP-ribose.The EMBO journal · 2025Article
- Monodisperse Chemical Oligophosphorylation of Peptides via Protected Oligophosphorimidazolide Reagents.Angewandte Chemie (International ed. in English) · 2025Article
- Site-specifically Phosphorylated Hsp90C-terminal Domain Variants Provide Access to Deciphering the Chaperone Code.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Reversible protein phosphorylation is a central signaling mechanism in eukaryotes. Although mass-spectrometry-based phosphoproteomics has become routine, identification of non-canonical phosphorylation has remained a challenge. Here we report a tailored workflow to detect and reliably assign protein pyrophosphorylation in two human cell lines, providing, to our knowledge, the first direct evidence of endogenous protein pyrophosphorylation. We manually validated 148 pyrophosphosites across 71 human proteins, the most heavily pyrophosphorylated of which were the nucleolar proteins NOLC1 and TCOF1. Detection was consistent with previous biochemical evidence relating the installation of the modification to inositol pyrophosphates (PP-InsPs). When the biosynthesis of PP-InsPs was perturbed, proteins expressed in this background exhibited no signs of pyrophosphorylation. Disruption of PP-InsP biosynthesis also significantly reduced rDNA transcription, potentially by lowering pyrophosphorylation on regulatory proteins NOLC1, TCOF1 and UBF1. Overall, protein pyrophosphorylation emerges as an archetype of non-canonical phosphorylation and should be considered in future phosphoproteomic analyses.
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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.