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Publication : Shedding of epithin/PRSS14 is induced by TGF-β and mediated by tumor necrosis factor-α converting enzyme.

First Author  Lee HS Year  2014
Journal  Biochem Biophys Res Commun Volume  452
Issue  4 Pages  1084-90
PubMed ID  25245289 Mgi Jnum  J:220081
Mgi Id  MGI:5632218 Doi  10.1016/j.bbrc.2014.09.055
Citation  Lee HS, et al. (2014) Shedding of epithin/PRSS14 is induced by TGF-beta and mediated by tumor necrosis factor-alpha converting enzyme. Biochem Biophys Res Commun 452(4):1084-90
abstractText  Epithin/PRSS14, a type II transmembrane serine protease, plays critical roles in cancer metastasis. Previously, we have reported that epithin/PRSS14 undergoes ectodomain shedding in response to phorbol myristate acetate (PMA) stimulation. In this study, we show that transforming growth factor-beta (TGF-beta) induces rapid epithin/PRSS14 shedding through receptor mediated pathway in 427.1.86 thymoma cells. Tumor necrosis factor-alpha converting enzyme (TACE) is responsible for this shedding. Amino acid sequence encompassing the putative shedding cleavage site of epithin/PRSS14 exhibit strong homology to the cleavage site of l-selectin, a known TACE substrate. TACE inhibitor, TAPI-0 and TACE siRNA greatly reduced TGF-beta-induced epithin/PRSS14 shedding. TGF-beta treatment induces translocation of intracellular pool of TACE to the membrane where epithin/PRSS14 resides. These findings suggest that TGF-beta induces epithin/PRSS14 shedding by mediating translocation of epithin/PRSS14 sheddase, TACE, to the membrane.
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