Proteomic and protein interaction network analysis of human T lymphocytes during cell-cycle entry

Stephen J. Orr, Daniel R. Boutz, Rong Wang, Constantinos Chronis, Nicholas C. Lea, Thivyan Thayaparan, Emma Hamilton, Hanna Milewicz, Eric Blanc, Ghulam J. Mufti, Edward M. Marcotte, N. Shaun B. Thomas

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Regulating the transition of cells such as T lymphocytes from quiescence (G 0) into an activated, proliferating state involves initiation of cellular programs resulting in entry into the cell cycle (proliferation), the growth cycle (blastogenesis, cell size) and effector (functional) activation. We show the first proteomic analysis of protein interaction networks activated during entry into the first cell cycle from G 0. We also provide proof of principle that blastogenesis and proliferation programs are separable in primary human T cells. We employed a proteomic profiling method to identify large-scale changes in chromatin/nuclear matrix-bound and unbound proteins in human T lymphocytes during the transition from G 0 into the first cell cycle and mapped them to form functionally annotated, dynamic protein interaction networks. Inhibiting the induction of two proteins involved in two of the most significantly upregulated cellular processes, ribosome biogenesis (eIF6) and hnRNA splicing (SF3B2/SF3B4), showed, respectively, that human T cells can enter the cell cycle without growing in size, or increase in size without entering the cell cycle.

Original languageEnglish (US)
Article number573
JournalMolecular Systems Biology
Volume8
DOIs
StatePublished - 2012

Keywords

  • cell cycle
  • cell size
  • mass spectrometry
  • proteomics
  • T cells

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)
  • Applied Mathematics

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