The S100A6 calcium-binding protein regulates endothelial cell-cycle progression and senescence

Endothelial Cell Biology Unit, School of Molecular & Cellular Biology, LIGHT Laboratories, University of Leeds, Clarendon Way, Leeds, LS2 9JT, UK.
FEBS Journal (Impact Factor: 3.99). 10/2012; 279(24). DOI: 10.1111/febs.12044
Source: PubMed

ABSTRACT Endothelial cells regulate many aspects of vascular physiology including vasculogenesis and angiogenesis. The S100 family of calcium-binding protein regulates many aspects of cell function but their roles in vascular physiology are less well understood. Herein, we investigated the expression and function of S100-related family members in endothelial cells. Analysis of total endothelial mRNAs using a human gene chip array revealed significant gene expression of the S100 calcium-binding protein family members S100A6, S100A10, S100A11 and S100A13. We examined the expression and functional properties of the major S100 family member, S100A6, in vascular endothelial cells. Comparison of primary and transformed human cells revealed significant differences in S100A6 protein levels. In primary human endothelial cells, S100A6 was present in both the nucleus and cytoplasm. To assess the function of endothelial S100A6, we depleted protein levels using RNA interference and this caused increased cell cycle arrest in the G2/M phase under different conditions. S100A6 depletion caused a decrease in both CDK1 and phospho-CDK1 levels which are essential for eukaryote cell cycle progression. S100A6 depletion also decreased CDK1, cyclin A1 and cyclin B gene expression with effects on cell cycle progression. Depletion of endothelial S100A6 levels also elevated β-galactosidase expression which is an important hallmark of cellular senescence and exit from the mammalian cell cycle. We thus propose that S100A6 has an important role in regulating endothelial commitment to and progression through the cell cycle. © 2012 The Authors Journal compilation © 2012 FEBS.

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