Tumor-associated protein SPIK/TATI suppresses serine protease dependent cell apoptosis.
Serine protease dependent cell apoptosis (SPDCA) is a recently described caspase independent innate apoptotic pathway. It differs from the traditional caspase dependent apoptotic pathway in that serine proteases, not caspases, are critical to the apoptotic process. The mechanism of SPDCA is still unclear and further investigation is needed to determine any role it may play in maintaining cellular homeostasis and development of disease. The current knowledge about this pathway is limited only to the inhibitory effects of some serine protease inhibitors. Synthetic agents such as pefabloc, AEBSF and TPCK can inhibit this apoptotic process in cultured cells. There is little known, however, about biologically active agents available in the cell which can inhibit SPDCA. Here, we show that over-expression of a cellular protein called serine protease inhibitor Kazal (SPIK/TATI/PSTI) results in a significant decrease in cell susceptibility to SPDCA, suggesting that SPIK is an apoptosis inhibitor suppressing this pathway of apoptosis. Previous work has associated SPIK and cancer development, indicating that this finding will help to open the doorway for further study on the mechanism of SPDCA and the role it may play in cancer development.
Lu
Xuanyong
X
Drexel Institute for Biotechnology and Virology Research, Department of Microbiology and Immunology, College of Medicine, Drexel University, 3805 Old Easton Road, Doylestown, PA 18902, USA. xl34@drexel.edu
Lamontagne
Jason
J
Lu
Felix
F
Block
Timothy M
TM
D017209:Apoptosis / Q000187:drug effects*; D061945:Caspase Inhibitors; D020169:Caspases / Q000502:physiology; D045744:Cell Line, Tumor; D006367:HeLa Cells; D006801:Humans; D012697:Serine Endopeptidases / Q000502:physiology; D015842:Serine Proteinase Inhibitors / Q000502:physiology*; D014359:Trypsin Inhibitor, Kazal Pancreatic / Q000378:metabolism*
D061945:Caspase Inhibitors; D015842:Serine Proteinase Inhibitors; D014359:Trypsin Inhibitor, Kazal Pancreatic; D012697:Serine Endopeptidases; D020169:Caspases