Global and Site-Specific Effect of Phosphorylation on Protein Turnover

0539825 - ÚMG 2022 RIV US eng J - Článek v odborném periodiku
Wu, C. - Ba, Q. - Lü, D. - Li, W. - Šalovská, Barbora - Hou, P. - Mueller, T. - Rosenberger, G. - Gao, E. - Di, Y. - Zhou, H. - Fornasiero, E.F. - Liu, Y.
Global and Site-Specific Effect of Phosphorylation on Protein Turnover.
Developmental Cell. Roč. 56, č. 1 (2021), s. 111-124. ISSN 1534-5807. E-ISSN 1878-1551
Institucionální podpora: RVO:68378050
Klíčová slova: data-independent acquisition * cell-culture * dynamics * quantification * identification * proteomics * stability * reveals * peptide * silac
Obor OECD: Cell biology
Impakt faktor: 13.417, rok: 2021
Způsob publikování: Omezený přístup
https://www.cell.com/developmental-cell/fulltext/S1534-5807(20)30875-3?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1534580720308753%3Fshowall%3Dtrue

To date, the effects of specific modification types and sites on protein lifetime have not been systematically illustrated. Here, we describe a proteomic method, DeltaSILAC, to quantitatively assess the impact of site-specific phosphorylation on the turnover of thousands of proteins in live cells. Based on the accurate and reproducible mass spectrometry-based method, a pulse labeling approach using stable isotope-labeled amino acids in cells (pSILAC), phosphoproteomics, and a unique peptide-level matching strategy, our DeltaSILAC profiling revealed a global, unexpected delaying effect of many phosphosites on protein turnover. We further found that phosphorylated sites accelerating protein turnover are functionally selected for cell fitness, enriched in Cyclin-dependent kinase substrates, and evolutionarily conserved, whereas the glutamic acids surrounding phosphosites significantly delay protein turnover. Our method represents a generalizable approach and provides a rich resource for prioritizing the effects of phosphorylation sites on protein lifetime in the context of cell signaling and disease biology.
Trvalý link: http://hdl.handle.net/11104/0317525