title: Shedding of epithin/PRSS14 is induced by TGF-β and mediated by tumor necrosis factor-α converting enzyme.
abstract: 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-β (TGF-β) induces rapid epithin/PRSS14 shedding through receptor mediated pathway in 427.1.86 thymoma cells. Tumor necrosis factor-α 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-β-induced epithin/PRSS14 shedding. TGF-β treatment induces translocation of intracellular pool of TACE to the membrane where epithin/PRSS14 resides. These findings suggest that TGF-β induces epithin/PRSS14 shedding by mediating translocation of epithin/PRSS14 sheddase, TACE, to the membrane.
authors.affiliation: School of Biological Sciences, Seoul National University, Seoul 151-747, Republic of Korea.
authors.forename: Hyo Seon
authors.initials: HS
authors.lastname: Lee
authors.affiliation: School of Biological Sciences, Seoul National University, Seoul 151-747, Republic of Korea.
authors.forename: Bo Mi
authors.initials: BM
authors.lastname: Park
authors.affiliation: School of Biological Sciences, Seoul National University, Seoul 151-747, Republic of Korea.
authors.forename: Youngkyung
authors.initials: Y
authors.lastname: Cho
authors.affiliation: Department of Biological Sciences, Inha University, Incheon 402-751, Republic of Korea.
authors.forename: Sauryang
authors.initials: S
authors.lastname: Kim
authors.affiliation: School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Chungho
authors.initials: C
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, Inha University, Incheon 402-751, Republic of Korea.
authors.forename: Moon Gyo
authors.initials: MG
authors.lastname: Kim
authors.affiliation: School of Biological Sciences, Seoul National University, Seoul 151-747, Republic of Korea. Electronic address: depark@snu.ac.kr.
authors.forename: Dongeun
authors.initials: D
authors.lastname: Park
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism*; D000072198:ADAM17 Protein; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D021381:Protein Transport / Q000502:physiology; D012697:Serine Endopeptidases / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D016212:Transforming Growth Factor beta; D012697:Serine Endopeptidases; C118992:St14 protein, mouse; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606463:Adam17 protein, mouse
keywords: Ectodomain shedding; Epithin; TGF-β; Tumor necrosis factor-α converting enzyme (TACE)