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PMID:19162005

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Citation

Fosbrink, M, Cudrici, C, Tegla, CA, Soloviova, K, Ito, T, Vlaicu, S, Rus, V, Niculescu, F and Rus, H (2009) Response gene to complement 32 is required for C5b-9 induced cell cycle activation in endothelial cells. Exp. Mol. Pathol. 86:87-94

Abstract

Proliferation of vascular endothelial cells (EC) and smooth muscle cells (SMC) is a critical event in angiogenesis and atherosclerosis. We previously showed that the C5b-9 assembly during complement activation induces cell cycle in human aortic EC (AEC) and SMC. C5b-9 can induce the expression of Response Gene to Complement (RGC)-32 and over expression of this gene leads to cell cycle activation. Therefore, the present study was carried out to test the requirement of endogenous RGC-32 for the cell cycle activation induced by C5b-9 by knocking-down its expression using siRNA. We identified two RGC-32 siRNAs that can markedly reduce the expression of RGC-32 mRNA in AEC. RGC-32 silencing in these cells abolished DNA synthesis induced by C5b-9 and serum growth factors, indicating the requirement of RGC-32 activity for S-phase entry. RGC-32 siRNA knockdown also significantly reduced the C5b-9 induced CDC2 activation and Akt phosphorylation. CDC2 does not play a role in G1/S transition in HeLa cells stably overexpressing RGC-32. RGC-32 was found to physically associate with Akt and was phosphorylated by Akt in vitro. Mutation of RGC-32 protein at Ser 45 and Ser 47 prevented Akt mediated phosphorylation. In addition, RGC-32 was found to regulate the release of growth factors from AEC. All these data together suggest that cell cycle induction by C5b-9 in AEC is RGC-32 dependent and this is in part through regulation of Akt and growth factor release.

Links

PubMed PMC2699899 Online version:10.1016/j.yexmp.2008.12.005

Keywords

Adult; Angiogenesis Inducing Agents/metabolism; CDC2 Protein Kinase/metabolism; Cell Cycle/drug effects; Cell Cycle Proteins/genetics; Cell Cycle Proteins/metabolism; Complement Membrane Attack Complex/pharmacology; Cyclin-Dependent Kinase Inhibitor p27/metabolism; Endothelial Cells/cytology; Endothelial Cells/drug effects; Endothelial Cells/enzymology; Enzyme Activation/drug effects; HeLa Cells; Humans; Membrane Proteins/metabolism; Muscle Proteins/genetics; Muscle Proteins/metabolism; Nerve Tissue Proteins/genetics; Nerve Tissue Proteins/metabolism; Nuclear Proteins/metabolism; Phosphorylation/drug effects; Protein Binding/drug effects; Proto-Oncogene Proteins c-akt/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:AKT1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9H4X1

F

Seeded From UniProt

complete

HUMAN:RGCC

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P31749

F

Seeded From UniProt

complete

HUMAN:RGCC

involved_in

GO:0001819: positive regulation of cytokine production

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:RGCC

involved_in

GO:0001818: negative regulation of cytokine production

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:RGCC

involved_in

GO:0006956: complement activation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:RGCC

involved_in

GO:0045840: positive regulation of mitotic nuclear division

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:RGCC

involved_in

GO:0045737: positive regulation of cyclin-dependent protein serine/threonine kinase activity

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:RGCC

involved_in

GO:1900087: positive regulation of G1/S transition of mitotic cell cycle

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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