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The role of C5b-9 terminal complement complex in activation of the cell cycle and transcription

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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 doses 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 proctection from apoptosis.

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Author notes

  1. Florin Niculescu

    Present address: Department of Pathology, University of Maryland School of Medicine, 10 South Pine Street, 21201, Baltimore, MD

Authors and Affiliations

  1. Toxicology Program, University of Maryland, Baltimore, MD

    Matthew Fosbrink

  2. Department of Pathology, University of Maryland School of Medicine, 10 South Pine Street, 21201, Baltimore, MD

    Matthew Fosbrink & Horea Rus

  3. Department of Neurology, University of Maryland School of Medicine and Veterans Administration Maryland Health Care System, Multiple Sclerosis Center of Excellence, Baltimore, MD

    Horea Rus

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  2. Florin Niculescu
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  3. Horea Rus
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Fosbrink, M., Niculescu, F. & Rus, H. The role of C5b-9 terminal complement complex in activation of the cell cycle and transcription. Immunol Res 31, 37–46 (2005). https://doi.org/10.1385/IR:31:1:37

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