title: Human cathepsin W, a cysteine protease predominantly expressed in NK cells, is mainly localized in the endoplasmic reticulum.
abstract: Human cathepsin W (also called lymphopain) is a recently described papain-like cysteine protease of unknown function whose gene expression was found to be restricted to cytotoxic cells. Here we demonstrate that cathepsin W is expressed predominantly in NK cells and, to a lesser extent, in CTLs. Quantitative RT-PCR revealed that NK cells contained approximately 21 times more cathepsin W transcript than CTLs. The predominant expression of cathepsin W in NK cells was further confirmed by Western blot analysis and immunohistochemistry. IL-2-mediated stimulation of NK cells and CTLs revealed a stronger up-regulation of the cathepsin W gene and protein expression in NK cells (7-fold) than in CTLs (2-fold). Transfection experiments of HeLa cells and biochemical analyses revealed that cathepsin W is exclusively "high mannose-type" glycosylated and is mainly targeted to the endoplasmic reticulum (ER). Interestingly, the ER localization of cathepsin W was also found in NK cells, in which colocalization studies revealed an overlapping staining of cathepsin W and Con A, an ER-specific lectin. Furthermore, subcellular fractionation of cathepsin W-expressing cells confirmed the ER localization and showed that cathepsin W is membrane associated. Based on the results of this study, cathepsin W might represent a putative component of the ER-resident proteolytic machinery. The constitutive expression in NK cells and the stronger up-regulation of cathepsin W by IL-2 in NK cells than CTLs suggest that cathepsin W is not just a marker of cytotoxic cells but is, rather, specifically expressed in NK cells.
authors.affiliation: Department of Human Genetics, Mount Sinai School of Medicine, New York, NY 10029, USA. thomas.wex@medizin-uni-magdeburg.de
authors.forename: T
authors.initials: T
authors.lastname: Wex
authors.forename: F
authors.initials: F
authors.lastname: Bühling
authors.forename: H
authors.initials: H
authors.lastname: Wex
authors.forename: D
authors.initials: D
authors.lastname: Günther
authors.forename: P
authors.initials: P
authors.lastname: Malfertheiner
authors.forename: E
authors.initials: E
authors.lastname: Weber
authors.forename: D
authors.initials: D
authors.lastname: Brömme
mesh_terms: D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000737:chemistry; D015153:Blotting, Western; D056664:Cathepsin W; D002403:Cathepsins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002999:Clone Cells; D003546:Cysteine Endopeptidases / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D004790:Enzyme Induction / Q000276:immunology; D006367:HeLa Cells; D006801:Humans; D007106:Immune Sera / Q000096:biosynthesis / Q000737:chemistry; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000201:enzymology* / Q000378:metabolism; D013347:Subcellular Fractions / Q000201:enzymology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000201:enzymology / Q000378:metabolism; D014162:Transfection
chemical_list: D000911:Antibodies, Monoclonal; D007106:Immune Sera; D007376:Interleukin-2; D002403:Cathepsins; C534187:CTSW protein, human; D056664:Cathepsin W; D003546:Cysteine Endopeptidases