Proteome Half-Life Dynamics in Living Human Cells

In times of stress, long-lived proteins increase their durability. Cells remove proteins by two processes: degradation and dilution due to cell growth. The balance between these basic processes is poorly understood. We addressed this by developing an accurate and noninvasive method for measuring protein half-lives, called “bleach-chase,” that is applicable to fluorescently tagged proteins. Assaying 100 proteins in living human cancer cells showed half-lives that ranged between 45 minutes and 22.5 hours. A variety of stresses that stop cell division showed the same general effect: Long-lived proteins became longer-lived, whereas short-lived proteins remained largely unaffected. This effect is due to the relative strengths of degradation and dilution and suggests a mechanism for differential killing of rapidly growing cells by growth-arresting drugs. This approach opens a way to understand proteome half-life dynamics in living cells.

• Publication year

  2011

• Venue

  Science

• Publication date

  2011-02-11

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1126/science.1199784PMID 21233346
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• *These authors contributed equally to this work.

  2012cited by this paper
• Dynamic Proteomics of Individual Cancer Cells in Response to a Drug

  2008cited by this paper
• Global Protein Stability Profiling in Mammalian Cells

  2008cited by this paper
• Effects of dependence in high-dimensional multiple testing problems

  2008cited by this paper
• Introduction to systems biology.

  2007cited by this paper
• Strategy of Transcription Regulation in the Budding Yeast

  2007cited by this paper
• Generation of a fluorescently labeled endogenous protein library in living human cells

  2007cited by this paper
• An Introduction to Systems Biology Design Principles of Biological Circuits

  2007cited by this paper
• Ubiquitin ligases: cell-cycle control and cancer

  2006cited by this paper
• Topoisomerase I inhibitors: camptothecins and beyond

  2006cited by this paper
• Proteolysis: from the lysosome to ubiquitin and the proteasome

  2005cited by this paper
• IL-13受体α2降低血吸虫病肉芽肿的炎症反应并延长宿主存活时间[英]/Mentink-Kane MM,Cheever AW，Thompson RW，et al//Proc Natl Acad Sci U S A

  2005cited by this paper
• Genetically targeted chromophore-assisted light inactivation

  2003cited by this paper
• Dynamics of Protein Turnover, a Missing Dimension in Proteomics*

  2002cited by this paper
• The ubiquitin-proteasome pathway and pathogenesis of human diseases.

  1999cited by this paper
• The ubiquitin system.

  1998cited by this paper
• Chromophore-assisted light inactivation and self-organization of microtubules and motors.

  1998cited by this paper
• Gratuitous overexpression of genes in Escherichia coli leads to growth inhibition and ribosome destruction

  1995cited by this paper
• Construction of a GAL1-regulated yeast cDNA expression library and its application to the identification of genes whose overexpression causes lethality in yeast.

  1992cited by this paper
• Proteins

  1987cited by this paper
• Genetics

  1981cited by this paper
• Control of enzyme levels in animal tissues.

  1970cited by this paper
• [The kinetics of the biosynthesis of beta-galactosidase in Escherichia coli as a function of growth].

  1952cited by this paper

• Shielded by the dead: how killed bacteria shape the dynamics and evolution of innate immunity

  2026cites this paper
• Peptide turnover prediction using transformer architectures on large-scale time-series proteomic data

  2026cites this paper
• Memory from variability: Heritable short-term cellular memory emerges from stochastic biochemical reaction networks

  2026cites this paper
• Leveraging Twin Information for Inference of Gene Regulatory Networks

  2026cites this paper
• A near-complete map of human cytosolic degrons and their relevance for disease

  2026cites this paper
• Natural Killer Cell Receptor Signaling and Activation Depend on Cell Cycle Stages

  2025influential citation
• Inherited or produced? Inferring protein production kinetics when protein counts are shaped by a cell’s division history

  2025cites this paper
• Deuterium labeling enables proteome wide turnover kinetics analysis in cell culture

  2025cites this paper
• Gene expression dynamics before and after zygotic gene activation in Drosophila early embryogenesis

  2025cites this paper
• Concentration buffering and noise reduction in non-equilibrium phase-separating systems.

  2025cites this paper
• A model of Notch signalling control of angiogenesis: Evidence of a role for Notch ligand heterodimerization

  2025cites this paper
• Mathematical Models of Topically and Intravitreally Applied Ranibizumab

  2025cites this paper
• Uncovering dynamic transcriptional regulation of methanogenesis via single-cell imaging of archaeal gene expression

  2025cites this paper
• Clone copy number diversity is linked to survival in lung cancer

  2025cites this paper
• A complete map of human cytosolic degrons and their relevance for disease

  2025cites this paper
• Selection of specific and efficient siRNAs in new cellular model for Hutchinson-Gilford progeria syndrome therapy

  2025cites this paper
• Mechanistic computational modeling of sFLT1 secretion dynamics

  2025cites this paper
• Comparative CRISPRi screens reveal a human stem cell dependence on mRNA translation-coupled quality control

  2025cites this paper
• Multiscale mathematical model-informed reinforcement learning optimizes combination treatment scheduling in glioblastoma evolution.

  2025cites this paper
• Deuterium labeling enables proteome-wide turnover kinetics analysis in cell culture

  2025cites this paper
• Mechanistic computational modeling of sFLT1 secretion dynamics

  2025cites this paper
• Impact of protein degradation and cell growth on mammalian proteomes

  2025cites this paper
• Biological Processes as Exploratory Dynamics.

  2025cites this paper
• Biological Processes as Exploratory Dynamics

  2025cites this paper
• Fundamental errors in RNA velocity arising from the omission of cell growth

  2025cites this paper
• Screening radiation-differentially expressed circular RNAs and establishing dose classification models in the human lymphoblastoid cell line AHH-1

  2024cites this paper
• Cellular Resiliency and Survival of a Neuro-2a Cell Line Under Extreme Stress.

  2024cites this paper
• Prediction of Protein Half-lives from Amino Acid Sequences by Protein Language Models

  2024cites this paper
• Systematic identification of 20S proteasome substrates

  2024cites this paper
• The Chemical Reactivity of Membrane Lipids

  2024cites this paper
• Degrees of freedom: temperature's influence on developmental rate.

  2024cites this paper
• CRL3ARMC5 ubiquitin ligase and Integrator phosphatase form parallel mechanisms to control early stages of RNA Pol II transcription

  2024cites this paper
• Nuclear release of eIF1 globally increases stringency of start-codon selection to preserve mitotic arrest physiology

  2024influential citation
• Understanding the Role of ATP Release through Connexins Hemichannels during Neurulation

  2023cites this paper
• Regulation of angiotensin-converting enzyme 2 isoforms by type 2 inflammation and viral infection in human airway epithelium

  2023cites this paper
• Multiparametric senescent cell phenotyping reveals targets of senolytic therapy in the aged murine skeleton

  2023cites this paper
• Multiparametric senescent cell phenotyping reveals CD24 osteolineage cells as targets of senolytic therapy in the aged murine skeleton

  2023cites this paper
• The one-message-per-cell-cycle rule: A conserved minimum transcription level for essential genes

  2023cites this paper
• An out‐of‐equilibrium definition of protein turnover

  2023cites this paper
• A new model of Notch signalling: Control of Notch receptor cis-inhibition via Notch ligand dimers

  2023cites this paper
• A multiscale model of the role of microenvironmental factors in cell segregation and heterogeneity in breast cancer development

  2023cites this paper
• Quantitative intravital imaging for real-time monitoring of pancreatic tumor cell hypoxia and stroma in an orthotopic mouse model

  2023cites this paper
• The one-message-per-cell-cycle rule: A conserved minimum transcription level for essential genes

  2023cites this paper
• Predicting Protein Shelf Lives from Mean First Passage Times

  2022cites this paper
• The fiber diameter traits of Tibetan cashmere goats are governed by the inherent differences in stress, hypoxic, and metabolic adaptations: an integrative study of proteome and transcriptome

  2022cites this paper
• Cancer therapy with immune checkpoint inhibitor and CSF-1 blockade: A mathematical model.

  2022cites this paper
• Loss of N-terminal acetyltransferase A activity induces thermally unstable ribosomal proteins and increases their turnover in Saccharomyces cerevisiae

  2022cites this paper
• Dynamics and consequences of the HTLV-1 proviral plus-strand burst

  2022cites this paper
• PGE2‐EP3 axis promotes brown adipose tissue formation through stabilization of WTAP RNA methyltransferase

  2022cites this paper
• Protein turnover models for LC-MS data of heavy water metabolic labeling

  2022cites this paper
• Conserved degronome features governing quality control associated proteolysis

  2022cites this paper
• Episome-Based Gene Expression Modulation Platform in the Model Diatom Phaeodactylum tricornutum.

  2022cites this paper
• The Future Potential of Biosensors to Investigate the Gut-Brain Axis

  2022cites this paper
• Enhanced precision of circadian rhythm by output system.

  2022cites this paper
• Transient nuclear lamin A/C accretion aids in recovery from vapor nanobubble-induced permeabilisation of the plasma membrane

  2022cites this paper
• Increased cellular detoxification, cytoskeletal activities and protein transport explain physiological stress in a lagoon sponge.

  2021cites this paper
• JUMPt: Comprehensive Protein Turnover Modeling of In Vivo Pulse SILAC Data by Ordinary Differential Equations.

  2021cites this paper
• Bracovirus Sneaks Into Apoptotic Bodies Transmitting Immunosuppressive Signaling Driven by Integration-Mediated eIF5A Hypusination

  2021cites this paper
• Inverse Problem Reveals Conditions for Characteristic Retinal Degeneration Patterns in Retinitis Pigmentosa Under the Trophic Factor Hypothesis

  2021cites this paper
• Imaging Mass Spectrometry of Long‐Lived Proteins

  2021cites this paper
• In vivo assay and modelling of protein and mitochondrial turnover during aging

  2021cites this paper
• SPAAC Pulse-Chase: A Novel Click Chemistry-Based Method to Determine the Half-Life of Cellular Proteins

  2021cites this paper
• In-depth characterization of ubiquitin turnover in mammalian cells by fluorescence tracking.

  2021cites this paper
• Mathematical Models of Retinitis Pigmentosa: The Trophic Factor Hypothesis

  2021cites this paper
• Proteomic characterization of the human lens and Cataractogenesis

  2021cites this paper
• Synthetic multistability in mammalian cells

  2021cites this paper
• Simulating CXCR5 Dynamics in Complex Tissue Microenvironments

  2021cites this paper
• Simple Kinetic Models in Molecular Chronobiology.

  2021cites this paper
• Addressing Non-linear System Dynamics of Single-Strand RNA Virus–Host Interaction

  2021cites this paper
• The Origins of Phenotypic Heterogeneity in Cancer

  2021cites this paper
• A Systematic Protein Turnover Map for Decoding Protein Degradation

  2020cites this paper
• An in-silico human cell model reveals the influence of spatial organization on RNA splicing

  2020cites this paper
• One-shot analysis of translated mammalian lncRNAs with AHARIBO

  2020cites this paper
• IL-37 Causes Excessive Inflammation and Tissue Damage in Murine Pneumococcal Pneumonia

  2020cites this paper
• Integrated in silico and 3D in vitro model of macrophage migration in response to physical and chemical factors in the tumor microenvironment

  2020cites this paper
• Progesterone-induced Warburg Effect is Regulated by Cell-type-specific Interaction of Progesterone Receptor Membrane Component 1 and Hexokinases

  2020cites this paper
• Systematic quantification of the dynamics of newly synthesized proteins unveiling their degradation pathways in human cells

  2020cites this paper
• Species-specific developmental timing is associated with differences in protein stability in mouse and human

  2020cites this paper
• Decreased Expression of the Human Urea Transporter SLC14A1 in Bone is Induced by Cytokines and Stimulates Adipogenesis of Mesenchymal Progenitor Cells.

  2020cites this paper
• Interspecies differences in proteome turnover kinetics are correlated with lifespans and energetic demands.

  2020cites this paper
• Generation of PAX7 Reporter Cells to Investigate Skeletal Myogenesis from Human Pluripotent Stem Cells

  2020cites this paper
• Proteome Turnover in the Spotlight: Approaches, Applications & Perspectives.

  2020cites this paper
• Pharmacodynamic modeling of synergistic birinapant/paclitaxel interactions in pancreatic cancer cells

  2020cites this paper
• Alterations of GABA B receptors in the APP/PS1 mouse model of Alzheimer's disease.

  2020cites this paper
• The Oscillation Amplitude, Not the Frequency of Cytosolic Calcium, Regulates Apoptosis Induction

  2020influential citation
• Frequency domain analysis of fluctuations of mRNA and protein copy numbers within a cell lineage: theory and experimental validation

  2020cites this paper
• Species-specific pace of development is associated with differences in protein stability

  2020cites this paper
• Physics, Determinism, and the Brain

  2020cites this paper
• High-throughput and Deep-proteome Profiling by 16-plex Tandem Mass Tag Labeling Coupled with Two-dimensional Chromatography and Mass Spectrometry.

  2020cites this paper
• Viral-structured models of dividing cells shows cell-virus coexistence via viral load partitioning between cell progeny

  2020cites this paper
• Comparing Theories for the Maintenance of Late LTP and Long-Term Memory: Computational Analysis of the Roles of Kinase Feedback Pathways and Synaptic Reactivation

  2020cites this paper
• Strategies to investigate protein turnover with fluorescent protein reporters in eukaryotic organisms

  2020cites this paper
• Proteome Turnover in the Spotlight: Approaches, Applications, and Perspectives

  2020cites this paper
• The palette of techniques for cell cycle analysis

  2020cites this paper
• Crystallography of Metabolic Enzymes.

  2020cites this paper
• Interspecies Differences in Proteome Turnover Kinetics Are Correlated With Life Spans and Energetic Demands

  2020cites this paper
• Probing Protein Shelf Lives from Inverse Mean First Passage Times

  2019cites this paper
• Phenotypic delay in the evolution of bacterial antibiotic resistance: Mechanistic models and their implications

  2019cites this paper
• The relationship of body condition, superoxide dismutase and superoxide with sperm performance

  2019influential citation
• IL-37 Causes Excessive Inflammation and Tissue Damage in Murine Pneumococcal Pneumonia

  2019cites this paper