S100A6 (calcyclin) deficiency induces senescence-like changes in cell cycle, morphology and functional characteristics of mouse NIH 3T3 fibroblasts.
S100A6 (calcyclin) is a calcium binding protein with two EF-hand structures expressed mostly in fibroblasts and epithelial cells. We have established a NIH 3T3 fibroblast cell line stably transfected with siRNA against S100A6 to examine the effect of S100A6 deficiency on non-transformed cell physiology. We found that NIH 3T3 fibroblasts with decreased level of S100A6 manifested altered cell morphology and proliferated at a much slower pace than the control cells. Cell cycle analysis showed that a large population of these cells lost the ability to respond to serum and persisted in the G0/G1 phase. Furthermore, fibroblasts with diminished S100A6 level exhibited morphological changes and biochemical features of cellular senescence as revealed by beta-galactosidase and gelatinase assays. Also, S100A6 deficiency induced changes in the actin cytoskeleton and had a profound impact on cell adhesion and migration. Thus, we have shown that the S100A6 protein is involved in multiple aspects of fibroblast physiology and that its presence ensures normal fibroblast proliferation and function.
Słomnicki
Lukasz P
LP
Department of Molecular and Cellular Neurobiology, Nencki Institute of Experimental Biology, 3 Pasteur St, 02-093 Warsaw, Poland.
Leśniak
Wiesława
W
D000818:Animals; D002448:Cell Adhesion; D002453:Cell Cycle / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D016922:Cellular Senescence; D003599:Cytoskeleton / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D000075383:S100 Calcium Binding Protein A6; D009418:S100 Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism
D018797:Cell Cycle Proteins; D000075383:S100 Calcium Binding Protein A6; D009418:S100 Proteins; C489134:S100a6 protein, mouse