title: S100A6 (calcyclin) enhances the sensitivity to apoptosis via the upregulation of caspase-3 activity in Hep3B cells.
abstract: 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.
authors.affiliation: Laboratory of Cell Biology, Korea Research Institute of Bioscience and Biotechnology (KRIBB), P.O. Box 115, Deajeon 305-333, Republic of Korea.
authors.forename: Joung Hyuck
authors.initials: JH
authors.lastname: Joo
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Yoon
authors.forename: Joo Heon
authors.initials: JH
authors.lastname: Kim
authors.forename: Sang-Gi
authors.initials: SG
authors.lastname: Paik
authors.forename: Sung Ran
authors.initials: SR
authors.lastname: Min
authors.forename: Jong-Seok
authors.initials: JS
authors.lastname: Lim
authors.forename: In Seong
authors.initials: IS
authors.lastname: Choe
authors.forename: Inpyo
authors.initials: I
authors.lastname: Choi
authors.forename: Jae Wha
authors.initials: JW
authors.lastname: Kim
mesh_terms: 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
chemical_list: 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