title: Proteomic and protein interaction network analysis of human T lymphocytes during cell-cycle entry.
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.
authors.affiliation: Department of Haematological Medicine, Leukaemia Sciences Laboratories, Rayne Institute, King's College London, UK.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Orr
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Boutz
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.forename: Constantinos
authors.initials: C
authors.lastname: Chronis
authors.forename: Nicholas C
authors.initials: NC
authors.lastname: Lea
authors.forename: Thivyan
authors.initials: T
authors.lastname: Thayaparan
authors.forename: Emma
authors.initials: E
authors.lastname: Hamilton
authors.forename: Hanna
authors.initials: H
authors.lastname: Milewicz
authors.forename: Eric
authors.initials: E
authors.lastname: Blanc
authors.forename: Ghulam J
authors.initials: GJ
authors.lastname: Mufti
authors.forename: Edward M
authors.initials: EM
authors.lastname: Marcotte
authors.forename: N Shaun B
authors.initials: NS
authors.lastname: Thomas
mesh_terms: D002453:Cell Cycle / Q000235:genetics / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D002843:Chromatin / Q000378:metabolism; D016000:Cluster Analysis; D004268:DNA-Binding Proteins / Q000378:metabolism; D039642:Eukaryotic Initiation Factors / Q000378:metabolism / Q000502:physiology; D016193:G1 Phase / Q000502:physiology; D006801:Humans; D034521:Nuclear Matrix-Associated Proteins / Q000302:isolation & purification / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D060066:Protein Interaction Maps; D040901:Proteomics; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins / Q000378:metabolism / Q000502:physiology; D016192:Resting Phase, Cell Cycle / Q000502:physiology; D013601:T-Lymphocytes / Q000378:metabolism* / Q000502:physiology*
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; C109284:EIF6 protein, human; D039642:Eukaryotic Initiation Factors; D034521:Nuclear Matrix-Associated Proteins; D009687:Nuclear Proteins; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins; C486348:SF3B2 protein, human; C486347:SF3B4 protein, human; C512114:XIRP1 protein, human