title: The role of c5b-9 terminal complement complex in activation of the cell cycle and transcription.
abstract: Activation of the complement system plays an important role in innate and acquired immunity. Activation of complement and subsequent formation of C5b-9 channels on the surface of cellular membranes leads to cell lysis. When the number of channels assembled on the surface of nucleated cells is limited, C5b-9 does not cause lysis, but instead can induce cell-cycle progression by activating signal transduction pathways, transcription factors, and key components of the cell-cycle machinery. Cell-cycle induction by C5b-9 is dependent on the activation of phosphatidylinositol 3-kinase and the ERK1 pathway in a Gi protein-dependent manner. Cell-cycle activation is regulated, in part, by activation of proto-oncogene c-jun and AP1 DNA binding activity. C5b-9 induces sequential activation of CDK4 and CDK2, leading to G1/S-phase transition and cellular proliferation. RGC-32 is a novel gene whose expression is induced by C5b-9. RGC-32 may play a key role in cell-cycle activation by increasing cyclin B1-CDC2 activity. C5b-9-mediated cell-cycle activation plays an important role in cellular proliferation and protection from apoptosis.
authors.affiliation: Toxicology Program, University of Maryland, Baltimore, MD 21201, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Fosbrink
authors.forename: Florin
authors.initials: F
authors.lastname: Niculescu
authors.forename: Horea
authors.initials: H
authors.lastname: Rus
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D015938:Complement Membrane Attack Complex / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D015938:Complement Membrane Attack Complex; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas