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

Patrick Herr1, Johan Boström2, Eric Rullman2

  • 1Science for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, 171 76 Stockholm, Sweden; Weston Park Cancer Centre, Department of Oncology and Metabolism, University of Sheffield, S10 2RX Sheffield, England.

Molecular & Cellular Proteomics : MCP
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This study reveals how gene transcription and protein activity coordinate during the cell cycle. It identifies key proteins, like S-adenosylmethionine synthase, crucial for cell division and DNA replication.

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Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • The cell cycle is a fundamental biological process for cell proliferation.
  • Understanding the interplay between gene transcription and protein dynamics is crucial for cell cycle regulation.

Purpose of the Study:

  • To integrate proteome-wide and phosphoproteome-wide mass spectrometry data with gene transcription profiles.
  • To investigate cell cycle-dependent protein abundance, activity, and localization.
  • To identify proteins essential for cell viability and their roles in cell cycle progression.

Main Methods:

  • Proteome- and phospho-proteome-wide mass spectrometry profiling.
  • Comparison of protein dynamics with gene transcription data.
  • CRISPR/Cas9 survivability studies.
  • Analysis of phosphorylation events and protein solubility dynamics.

Main Results:

  • Identified transcriptionally regulated G2 mRNAs with post-mitotic protein expression shifts.
  • Highlighted proteins critical for cell viability through CRISPR/Cas9 screening.
  • Characterized cell cycle-dependent phosphorylation motifs and protein translocation.
  • Demonstrated nuclear translocation of S-adenosylmethionine synthase (MAT2A) post-G1/S-checkpoint.

Conclusions:

  • The study provides an integrated resource linking transcriptional regulation to protein dynamics across the cell cycle.
  • MAT2A's nuclear translocation is implicated in maintaining epigenetic histone methylation during DNA replication.
  • Novel insights into cell cycle regulation and the roles of specific proteins are presented.