Proteome half-life dynamics in living human cells

Science. 2011 Feb 11;331(6018):764-8. doi: 10.1126/science.1199784. Epub 2011 Jan 13.

Abstract

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 types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaphase-Promoting Complex-Cyclosome
  • Antineoplastic Agents / pharmacology*
  • Camptothecin / pharmacology
  • Cell Cycle Proteins / metabolism
  • Cell Death
  • Cell Division* / drug effects
  • Cell Line, Tumor
  • Cytoplasm / metabolism
  • Fluorescence
  • Half-Life
  • Humans
  • Light
  • Luminescent Proteins
  • Microscopy, Fluorescence
  • Proteins / metabolism*
  • Proteome / metabolism*
  • Stress, Physiological
  • Ubiquitin-Protein Ligase Complexes / metabolism

Substances

  • Antineoplastic Agents
  • Cell Cycle Proteins
  • Luminescent Proteins
  • Proteins
  • Proteome
  • Ubiquitin-Protein Ligase Complexes
  • Anaphase-Promoting Complex-Cyclosome
  • Camptothecin