S100A6 (calcyclin) enhances the sensitivity to apoptosis via the upregulation of caspase-3 activity in Hep3B cells.
S100A6 (calcyclin) is a small calcium-binding protein which has been implicated in several cellular processes such as cell cycle progression, cytoskeleton rearrangement, and exocytosis. Also the upregulation of S100A6 has been reported in a variety of tumors and linked to metastasis. However, exact intracellular roles of S100A6 related with apoptosis have not been clarified yet. Here we demonstrated that the upregulation of S100A6 enhances the cell death rate compared to the control under the apoptotic conditions. In exogenously S100A6 induced Hep3B cells, cell viability was significantly decreased compared with mock and S100A6-knockdown cells under calcium ionophore A23187 treatment. The exogenously introduced S100A6 significantly affected the caspase-3-like activity in programmed cell death through the enhanced caspase-3 expression, which was verified by promoter assay in wild or mutant S100A6-transfected Hep3B cells. Next, the promoter activity of caspase-3 was increased by 2.5-folds in wild-type S100A6-transfected cells compared to mutant 2 (E67K, mutant of EF-hand motif) or control. Our results suggest that S100A6 might be involved in the processing of apoptosis by modulating the transcriptional regulation of caspase-3.
Joo
Joung Hyuck
JH
Laboratory of Cell Biology, Korea Research Institute of Bioscience and Biotechnology (KRIBB), P.O. Box 115, Deajeon 305-333, Republic of Korea.
Yoon
Sun Young
SY
Kim
Joo Heon
JH
Paik
Sang-Gi
SG
Min
Sung Ran
SR
Lim
Jong-Seok
JS
Choe
In Seong
IS
Choi
Inpyo
I
Kim
Jae Wha
JW
D017209:Apoptosis / Q000502:physiology*; D000001:Calcimycin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000096:biosynthesis*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D006801:Humans; D007476:Ionophores / Q000494:pharmacology; D009154:Mutation; D011401:Promoter Regions, Genetic; D000075383:S100 Calcium Binding Protein A6; D009418:S100 Proteins / Q000235:genetics / Q000502:physiology*; D015854:Up-Regulation
D018797:Cell Cycle Proteins; D007476:Ionophores; D000075383:S100 Calcium Binding Protein A6; D009418:S100 Proteins; C055351:S100A6 protein, human; D000001:Calcimycin; D053148:Caspase 3; D002118:Calcium