title: Membrane attack by complement: the assembly and biology of terminal complement complexes.
abstract: Complement system activation plays an important role in both innate and acquired immunity. Activation of the complement and the subsequent formation of C5b-9 channels (the membrane attack complex) on the cell membranes lead to cell death. However, when the number of channels assembled on the surface of nucleated cells is limited, sublytic C5b-9 can induce cell cycle progression by activating signal transduction pathways and transcription factors and inhibiting apoptosis. This induction by C5b-9 is dependent upon the activation of the phosphatidylinositol 3-kinase/Akt/FOXO1 and ERK1 pathways in a Gi protein-dependent manner. C5b-9 induces sequential activation of CDK4 and CDK2, enabling the G1/S-phase transition and cellular proliferation. In addition, it induces RGC-32, a novel gene that plays a role in cell cycle activation by interacting with Akt and the cyclin B1-CDC2 complex. C5b-9 also inhibits apoptosis by inducing the phosphorylation of Bad and blocking the activation of FLIP, caspase-8, and Bid cleavage. Thus, sublytic C5b-9 plays an important role in cell activation, proliferation, and differentiation, thereby contributing to the maintenance of cell and tissue homeostasis.
authors.affiliation: Department of Neurology, School of Medicine, University of Maryland, 655 W. Baltimore Street, BRB 12-033, Baltimore, MD 21201, USA.
authors.forename: Cosmin A
authors.initials: CA
authors.lastname: Tegla
authors.forename: Cornelia
authors.initials: C
authors.lastname: Cudrici
authors.forename: Snehal
authors.initials: S
authors.lastname: Patel
authors.forename: Richard
authors.initials: R
authors.lastname: Trippe
authors.forename: Violeta
authors.initials: V
authors.lastname: Rus
authors.forename: Florin
authors.initials: F
authors.lastname: Niculescu
authors.forename: Horea
authors.initials: H
authors.lastname: Rus
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D051023:BH3 Interacting Domain Death Agonist Protein / Q000276:immunology / Q000378:metabolism; D016203:CDC2 Protein Kinase; D053181:Caspase 8 / Q000276:immunology / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000276:immunology / Q000378:metabolism; D002462:Cell Membrane / Q000276:immunology* / Q000378:metabolism; D015938:Complement Membrane Attack Complex / Q000276:immunology* / Q000378:metabolism; D019926:Cyclin B / Q000276:immunology / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2 / Q000276:immunology / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics / Q000378:metabolism; D018844:Cyclin-Dependent Kinases; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D016193:G1 Phase / Q000276:immunology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000276:immunology*; D048052:Mitogen-Activated Protein Kinase 3 / Q000276:immunology / Q000378:metabolism; D009124:Muscle Proteins / Q000276:immunology / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000276:immunology / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000276:immunology / Q000378:metabolism; D010766:Phosphorylation / Q000276:immunology; D051057:Proto-Oncogene Proteins c-akt / Q000276:immunology / Q000378:metabolism; D016196:S Phase / Q000276:immunology; D051025:bcl-Associated Death Protein / Q000276:immunology / Q000378:metabolism
chemical_list: D051023:BH3 Interacting Domain Death Agonist Protein; D016203:CDC2 Protein Kinase; D053181:Caspase 8; D018797:Cell Cycle Proteins; D015938:Complement Membrane Attack Complex; D019926:Cyclin B; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D048052:Mitogen-Activated Protein Kinase 3; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051025:bcl-Associated Death Protein; C494819:BAD protein, human; C494814:BID protein, human; C085126:FOXO1 protein, human; C115049:RGCC protein, human; C528899:CDK1 protein, human; C495894:CDK2 protein, human; C495900:CDK4 protein, human; C505530:CASP8 protein, human