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A 39 kDa fragment of endogenous ASK1 suggests specific cleavage not degradation by the proteasome
Author(s) -
Stordal Britta,
Davey Ross
Publication year - 2008
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1002/iub.24
Subject(s) - lactacystin , ask1 , proteasome , endogeny , transfection , apoptosis , biology , cleavage (geology) , kinase , microbiology and biotechnology , protein kinase a , cyclin dependent kinase 2 , biochemistry , proteasome inhibitor , gene , paleontology , fracture (geology)
Transfected human apoptosis signal‐regulating kinase 1 (ASK1) produces a 150 kDa protein. However, we have detected endogenous ASK1 predominantly as 39 and 50 kDa C‐terminal and 75 and 110 kDa N‐terminal fragments in a panel of nontransfected cancer cell lines and HUVEC endothelial cells. This suggests that in nonapoptotic cells, endogenous ASK1 protein is normally cleaved at a number of specific sites, some of which are in the kinase domain. Transfected ASK1 protein is known to be degraded by the proteasome. In contrast, the cleavage of endogenous ASK1 is independent of the proteasome as treatment with the proteasome inhibitor, lactacystin did not inhibit cleavage. Cisplatin treatment decreased the amount of 39 kDa C‐terminal ASK1 fragments in mutant p53 cell lines suggesting a decrease in cleavage associated with apoptosis. Transfected ASK1 may, therefore, not accurately reflect the role of endogenous ASK1. © 2008 IUBMB IUBMB Life, 60(3): 180–184, 2008