Cell Cycle Profiling Reveals Protein Oscillation, Phosphorylation, and Localization Dynamics

Mol Cell Proteomics. 2020 Apr;19(4):608-623. doi: 10.1074/mcp.RA120.001938. Epub 2020 Feb 12.


The cell cycle is a highly conserved process involving the coordinated separation of a single cell into two daughter cells. To relate transcriptional regulation across the cell cycle with oscillatory changes in protein abundance and activity, we carried out a proteome- and phospho-proteome-wide mass spectrometry profiling. We compared protein dynamics with gene transcription, revealing many transcriptionally regulated G2 mRNAs that only produce a protein shift after mitosis. Integration of CRISPR/Cas9 survivability studies further highlighted proteins essential for cell viability. Analyzing the dynamics of phosphorylation events and protein solubility dynamics over the cell cycle, we characterize predicted phospho-peptide motif distributions and predict cell cycle-dependent translocating proteins, as exemplified by the S-adenosylmethionine synthase MAT2A. Our study implicates this enzyme in translocating to the nucleus after the G1/S-checkpoint, which enables epigenetic histone methylation maintenance during DNA replication. Taken together, this data set provides a unique integrated resource with novel insights on cell cycle dynamics.

Keywords: Cell cycle; computational biology; phosphorylation; subcellular separation; systems biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle / genetics*
  • Cell Nucleus / metabolism
  • Gene Expression Profiling*
  • HeLa Cells
  • Humans
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Phosphorylation
  • Protein Transport
  • Proteome / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Subcellular Fractions / metabolism
  • Transcriptome / genetics


  • Neoplasm Proteins
  • Proteome
  • RNA, Messenger