ArticleProceedings of the National Academy of Sciences of the United States of America2024
Maximum entropy determination of mammalian proteome dynamics.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 3 citations in OpenAlex.
- CardamomOT: A mechanistic optimal transport-based framework for gene regulatory network inference, trajectory reconstruction and generative modeling.PLoS computational biology · 2026Article
- Polymicrobial Extracellular Vesicles Reduce the Innate Immune Response of Human Cystic Fibrosis Bronchial Epithelial Cells.Journal of extracellular biology · 2026Article
- Polymicrobial extracellular vesicles reduce the innate immune response of human cystic fibrosis bronchial epithelial cells.bioRxiv : the preprint server for biology · 2026Article
- Disentangling protein metabolic costs in human cells and tissues.PNAS nexus · 2025Article
- Physical modeling of embryonic transcriptomes identifies collective modes of gene expression.bioRxiv : the preprint server for biology · 2024Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Full understanding of proteostasis and energy utilization in cells will require knowledge of the fraction of cell proteins being degraded with different half-lives and their rates of synthesis. We therefore developed a method to determine such information that combines mathematical analysis of protein degradation kinetics obtained in pulse-chase experiments with Bayesian data fitting using the maximum entropy principle. This approach will enable rapid analyses of whole-cell protein dynamics in different cell types, physiological states, and neurodegenerative disease. Using it, we obtained surprising insights about protein stabilities in cultured cells normally and upon activation of proteolysis by mTOR inhibition and increasing cAMP or cGMP. It revealed that >90% of protein content in dividing mammalian cell lines is long-lived, with half-lives of 24 to 200 h, and therefore comprises much of the proteins in daughter cells. The well-studied short-lived proteins (half-lives < 10 h) together comprise <2% of cell protein mass, but surprisingly account for 10 to 20% of measurable newly synthesized protein mass. Evolution thus appears to have minimized intracellular proteolysis except to rapidly eliminate misfolded and regulatory proteins.
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Registered trials
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