title: Regulation of cathepsins S and L by cystatin F during maturation of dendritic cells.
abstract: In dendritic cells (DCs) cysteine cathepsins play a key role in antigen processing, invariant chain (Ii) cleavage and regulation of cell adhesion after maturation stimuli. Cystatin F, a cysteine protease inhibitor, is present in DCs in endosomal/lysosomal vesicles and thus has a potential to modulate cathepsin activity. In immature DCs cystatin F colocalizes with cathepsin S. After induction of DC maturation however, it is translocated into lysosomes and colocalizes with cathepsin L. The inhibitory potential of cystatin F depends on the properties of the monomer. We showed that the full-length monomeric cystatin F was a 12-fold stronger inhibitor of cathepsin S than the N-terminally processed cystatin F, whereas no significant difference in inhibition was observed for cathepsins L, H and X. Therefore, the role of cystatin F in regulating the main cathepsin S function in DCs, i.e. the processing of Ii, may depend on the form of the monomer present in endosomal/lysosomal vesicles. On the other hand, intact and truncated monomeric cystatin F are both potent inhibitors of cathepsin L and it is likely that cystatin F could regulate its activity in maturing, adherent DCs, controlling the processing of procathepsin X, which promotes cell adhesion via activation of Mac-1 (CD11b/CD18) integrin receptor.
authors.affiliation: Jožef Stefan Institute, Department of Biotechnology, Ljubljana, Slovenia.
authors.forename: Spela
authors.initials: S
authors.lastname: Magister
authors.forename: Nataša
authors.initials: N
authors.lastname: Obermajer
authors.forename: Bojana
authors.initials: B
authors.lastname: Mirković
authors.forename: Urban
authors.initials: U
authors.lastname: Svajger
authors.forename: Miha
authors.initials: M
authors.lastname: Renko
authors.forename: Adaleta
authors.initials: A
authors.lastname: Softić
authors.forename: Rok
authors.initials: R
authors.lastname: Romih
authors.forename: Jeff D
authors.initials: JD
authors.lastname: Colbert
authors.forename: Colin
authors.initials: C
authors.lastname: Watts
authors.forename: Janko
authors.initials: J
authors.lastname: Kos
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D056668:Cathepsin L / Q000378:metabolism*; D002403:Cathepsins / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D015891:Cystatins / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism*; D005260:Female; D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008297:Male
chemical_list: D014408:Biomarkers, Tumor; C116891:CST7 protein, human; D015891:Cystatins; D016177:Macrophage-1 Antigen; D002403:Cathepsins; C534281:CTSL protein, human; D056668:Cathepsin L; C028217:cathepsin S