Related Experiment Video
Updated: May 5, 2026
08:45
Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors
Published on: July 17, 2020
6.2K
Extensive protein pyrophosphorylation revealed in human cell lines
Jeremy A M Morgan1, Arpita Singh2,3, Leonie Kurz1,4
1Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany.
Nature Chemical Biology
|April 25, 2024
Summary
Scientists discovered protein pyrophosphorylation, a new type of protein modification. This finding provides the first direct evidence of this modification in human cells and highlights its role in cellular signaling.
Area of Science:
- Biochemistry
- Molecular Biology
- Cellular Signaling
Background:
- Reversible protein phosphorylation is a key eukaryotic signaling pathway.
- Identifying non-canonical phosphorylation modifications remains a significant challenge in phosphoproteomics.
Purpose of the Study:
- To develop and implement a workflow for detecting and assigning protein pyrophosphorylation.
- To provide the first direct evidence of endogenous protein pyrophosphorylation in human cells.
Main Methods:
- A tailored workflow was developed for detecting protein pyrophosphorylation.
- Mass-spectrometry-based phosphoproteomics was employed.
- Manual validation of identified pyrophosphosites was performed.
Main Results:
- The study provides the first direct evidence of endogenous protein pyrophosphorylation in human cell lines.
- 148 pyrophosphosites on 71 human proteins were manually validated, with NOLC1 and TCOF1 being heavily modified.
- Perturbation of inositol pyrophosphate (PP-InsP) biosynthesis abolished pyrophosphorylation and reduced rDNA transcription.
Conclusions:
- Protein pyrophosphorylation is a significant non-canonical phosphorylation event.
- The modification is linked to inositol pyrophosphates (PP-InsPs).
- Pyrophosphorylation may play a role in regulating rDNA transcription via proteins like NOLC1, TCOF1, and UBF1.
Related Concept Videos
01:02Phosphorylation
44.8K
The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
44.8K
02:54Protein Kinases and Phosphatases
12.1K
Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
12.1K
01:19Protein Dynamics in Living Cells
1.9K
Different fluorescence-based techniques are used to study the protein dynamics in living cells. These techniques include FRAP, FRET, and PET.
Fluorescent recovery after photobleaching (FRAP) is a fluorescent-protein-based detection technique used to quantify protein movement rates within the cell. This method exposes a small portion of the cell to an intense laser beam. The laser beam causes permanent photobleaching of the fluorophore-tagged proteins in the exposed region. As the bleached...
Fluorescent recovery after photobleaching (FRAP) is a fluorescent-protein-based detection technique used to quantify protein movement rates within the cell. This method exposes a small portion of the cell to an intense laser beam. The laser beam causes permanent photobleaching of the fluorophore-tagged proteins in the exposed region. As the bleached...
1.9K