Pervasive Protein Thermal Stability Variation during the Cell Cycle

Cell. 2018 May 31;173(6):1495-1507.e18. doi: 10.1016/j.cell.2018.03.053. Epub 2018 Apr 26.


Quantitative mass spectrometry has established proteome-wide regulation of protein abundance and post-translational modifications in various biological processes. Here, we used quantitative mass spectrometry to systematically analyze the thermal stability and solubility of proteins on a proteome-wide scale during the eukaryotic cell cycle. We demonstrate pervasive variation of these biophysical parameters with most changes occurring in mitosis and G1. Various cellular pathways and components vary in thermal stability, such as cell-cycle factors, polymerases, and chromatin remodelers. We demonstrate that protein thermal stability serves as a proxy for enzyme activity, DNA binding, and complex formation in situ. Strikingly, a large cohort of intrinsically disordered and mitotically phosphorylated proteins is stabilized and solubilized in mitosis, suggesting a fundamental remodeling of the biophysical environment of the mitotic cell. Our data represent a rich resource for cell, structural, and systems biologists interested in proteome regulation during biological transitions.

Keywords: cell cycle; proteomics; thermal proteome profiling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle*
  • Chromatin Assembly and Disassembly
  • Cluster Analysis
  • DNA / analysis*
  • HeLa Cells
  • Hot Temperature
  • Humans
  • Mass Spectrometry
  • Mitosis
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Protein Stability
  • Proteome / analysis*
  • Proteomics / methods*
  • RNA Polymerase II / metabolism
  • Solubility


  • Proteome
  • DNA
  • RNA Polymerase II