title: Time-course network analysis reveals TNF-α can promote G1/S transition of cell cycle in vascular endothelial cells.
abstract: BACKGROUND
  Tumor necrosis factor-alpha (TNF-α), a major inflammatory cytokine, is closely related to several cardiovascular pathological processes. However, its effects on the cell cycle of vascular endothelial cells (VECs) have been the subject of some controversy. To investigate the molecular mechanism underlying this process, we constructed time-course protein-protein interaction (PPI) networks of TNF-α induced regulation of cell cycle in VECs using microarray datasets and genome-wide PPI datasets. Then, we analyzed the topological properties of the responsive PPI networks and calculated the node degree and node betweenness centralization of each gene in the networks. We found that p21, p27 and cyclinD1, key genes of the G1/S checkpoint, are in the center of responsive PPI networks and their roles in PPI networks are significantly altered with induction of TNF-α. According to the following biological experiments, we proved that TNF-α can promote G(1)/S transition of cell cycle in VECs and facilitate the cell cycle activation induced by vascular endothelial growth factor.
  
  
  BACKGROUND
  shaoli@mail.tsinghua.edu.cn
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors.affiliation: MOE Key Laboratory of Bioinformatics and Bioinformatics Division, TNLIST, Department of Automation, Tsinghua University, Beijing 100084, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Chen
authors.forename: Jin
authors.initials: J
authors.lastname: Gu
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.forename: Shao
authors.initials: S
authors.lastname: Li
mesh_terms: D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism; D002455:Cell Division; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D011485:Protein Binding; D060066:Protein Interaction Maps; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C530104:CCND1 protein, human; C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27