Linking post-translational modifications and protein turnover by site-resolved protein turnover profiling.
Acetylation
B-Lymphocytes
/ cytology
Cell Line, Tumor
Half-Life
HeLa Cells
Humans
Phosphorylation
Protein Binding
Protein Interaction Mapping
Protein Processing, Post-Translational
Protein Stability
Proteins
/ genetics
Proteolysis
Proteome
/ classification
Proteomics
/ methods
Software
Ubiquitination
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
10 01 2022
10 01 2022
Historique:
received:
01
08
2021
accepted:
02
12
2021
entrez:
11
1
2022
pubmed:
12
1
2022
medline:
11
2
2022
Statut:
epublish
Résumé
Proteome-wide measurements of protein turnover have largely ignored the impact of post-translational modifications (PTMs). To address this gap, we employ stable isotope labeling and mass spectrometry to measure the turnover of >120,000 peptidoforms including >33,000 phosphorylated, acetylated, and ubiquitinated peptides for >9,000 native proteins. This site-resolved protein turnover (SPOT) profiling discloses global and site-specific differences in turnover associated with the presence or absence of PTMs. While causal relationships may not always be immediately apparent, we speculate that PTMs with diverging turnover may distinguish states of differential protein stability, structure, localization, enzymatic activity, or protein-protein interactions. We show examples of how the turnover data may give insights into unknown functions of PTMs and provide a freely accessible online tool that allows interrogation and visualisation of all turnover data. The SPOT methodology is applicable to many cell types and modifications, offering the potential to prioritize PTMs for future functional investigations.
Identifiants
pubmed: 35013197
doi: 10.1038/s41467-021-27639-0
pii: 10.1038/s41467-021-27639-0
pmc: PMC8748498
doi:
Substances chimiques
Proteins
0
Proteome
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
165Informations de copyright
© 2022. The Author(s).
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