Systematic analysis of proteome turnover in an organoid model of pancreatic cancer by dSILO
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Q Exactive HF
ORGANISM(S): Mus Musculus (ncbitaxon:10090)
SUBMITTER: 
Marko Jovanovic Christine Chio
PROVIDER: MSV000092498 | MassIVE | Fri Jul 21 13:10:00 BST 2023
REPOSITORIES: MassIVE
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Project description:Protein turnover rates severely decline in aging organisms, including C. elegans. However, limited information is available on turnover dynamics at the individual protein level during aging. We followed changes in protein turnover at one-day resolution using a multiple-pulse 15N-labeling and accurate mass spectrometry approach. Forty percent of the proteome shows gradual slowdown in turnover with age, while only few proteins show increased turnover. Decrease in protein turnover was consistent for the minority of functional protein subsets, including tubulins and vitellogenins, while for most functionally related protein pools randomly diverging turnover patterns were observed with age. Our data suggests severe dysregulation of protein turnover of the translation machinery, whereas protein turnover of UPS and antioxidant systems are well-preserved over time. Hence, we presume that maintenance of quality control mechanisms is a protective strategy in aging worms, although the ultimate proteome collapse is inescapable.
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Project description:The turnover measurement of proteins and proteoforms has been largely facilitated by the metabolic labeling coupled with mass spectrometry (MS), such as the dynamic Stable isotope labeling by amino acids in cell culture (SILAC) experiments, i.e., the dynamic SILAC or pSILAC approach. Very recent studies including ours have integrated post-translational modification (PTM) proteomic methodology, such as phosphoproteomics, with pSILAC experiments in steady-state systems and revealed the link between protein PTM and turnover on the proteome-scale. In this study, we present a novel pSILAC phosphoproteomic dataset in a dynamic process of cell starvation using data-independent acquisition mass spectrometry (DIA-MS). We further propose a “hypothesis-free”, time series data analysis strategy to interrogate how phosphorylation dynamically impact protein turnover. With this strategy, we discovered complex relationship between phosphorylation and protein turnover that was previously underexplored. Our results further revealed potential biological features including phosphorylation stoichiometry that are associated with the peptideform turnover of phosphorylation. Our data also suggested that phosphoproteomic abundance regulation during starvation tends to be not correlated with turnover diversity, underscoring the importance of studying PTM site-resolved turnover datasets in the future.
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Project description:Efficient protein turnover is essential for cellular homeostasis and organ function. Loss
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link between the turnover of individual proteasome subunits and the age-associated
decline in proteosome activity.
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