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Inhibitory properties of cystatin F and its localization in U937 promonocyte cells

Langerholc, T; Zavasnik-Bergant, V; Turk, B; Turk, V; Abrahamson, Magnus LU and Kos, J (2005) In The FEBS Journal 272(6). p.1535-1545
Abstract
Cystatin F is a recently discovered type II cystatin expressed almost exclusively in immune cells. It is present intracellularly in lysosome-like vesicles, which suggests a potential role in regulating papain-like cathepsins involved in antigen presentation. Therefore, interactions of cystatin F with several of its potential targets, cathepsins F, K, V, S, H, X and C, were studied in vitro. Cystatin F tightly inhibited cathepsins F, K and V with K-i values ranging from 0.17 nm to 0.35 nm, whereas cathepsins S and H were inhibited with 100-fold lower affinities (K-i approximate to 30 nm). The exopeptidases, cathepsins C and X were not inhibited by cystatin F. In order to investigate the biological significance of the inhibition data, the... (More)
Cystatin F is a recently discovered type II cystatin expressed almost exclusively in immune cells. It is present intracellularly in lysosome-like vesicles, which suggests a potential role in regulating papain-like cathepsins involved in antigen presentation. Therefore, interactions of cystatin F with several of its potential targets, cathepsins F, K, V, S, H, X and C, were studied in vitro. Cystatin F tightly inhibited cathepsins F, K and V with K-i values ranging from 0.17 nm to 0.35 nm, whereas cathepsins S and H were inhibited with 100-fold lower affinities (K-i approximate to 30 nm). The exopeptidases, cathepsins C and X were not inhibited by cystatin F. In order to investigate the biological significance of the inhibition data, the intracellular localization of cystatin F and its potential targets, cathepsins B, H, L, S, C and K, were studied by confocal microscopy in U937 promonocyte cells. Although vesicular staining was observed for all the enzymes, only cathepsins H and X were found to be colocalized with the inhibitor. This suggests that cystatin F in U937 cells may function as a regulatory inhibitor of proteolytic activity of cathepsin H or, more likely, as a protection against cathepsins misdirected to specific cystatin F containing endosomal/lysosomal vesicles. The finding that cystatin F was not colocalized with cystatin C suggests distinct functions for these two cysteine protease inhibitors in U937 cells. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
antigen presentation, cystatin, inhibition, cathepsin, cysteine protease
in
The FEBS Journal
volume
272
issue
6
pages
1535 - 1545
publisher
Federation of European Neuroscience Societies and Blackwell Publishing Ltd
external identifiers
  • pmid:15752368
  • wos:000227395200020
  • scopus:15944426682
ISSN
1742-464X
DOI
10.1111/j.1742-4658.2005.04594.x
language
English
LU publication?
yes
id
fc460e80-97d6-4f1c-ad40-1fe75c2c312b (old id 250549)
date added to LUP
2007-08-15 12:33:56
date last changed
2017-08-20 04:27:38
@article{fc460e80-97d6-4f1c-ad40-1fe75c2c312b,
  abstract     = {Cystatin F is a recently discovered type II cystatin expressed almost exclusively in immune cells. It is present intracellularly in lysosome-like vesicles, which suggests a potential role in regulating papain-like cathepsins involved in antigen presentation. Therefore, interactions of cystatin F with several of its potential targets, cathepsins F, K, V, S, H, X and C, were studied in vitro. Cystatin F tightly inhibited cathepsins F, K and V with K-i values ranging from 0.17 nm to 0.35 nm, whereas cathepsins S and H were inhibited with 100-fold lower affinities (K-i approximate to 30 nm). The exopeptidases, cathepsins C and X were not inhibited by cystatin F. In order to investigate the biological significance of the inhibition data, the intracellular localization of cystatin F and its potential targets, cathepsins B, H, L, S, C and K, were studied by confocal microscopy in U937 promonocyte cells. Although vesicular staining was observed for all the enzymes, only cathepsins H and X were found to be colocalized with the inhibitor. This suggests that cystatin F in U937 cells may function as a regulatory inhibitor of proteolytic activity of cathepsin H or, more likely, as a protection against cathepsins misdirected to specific cystatin F containing endosomal/lysosomal vesicles. The finding that cystatin F was not colocalized with cystatin C suggests distinct functions for these two cysteine protease inhibitors in U937 cells.},
  author       = {Langerholc, T and Zavasnik-Bergant, V and Turk, B and Turk, V and Abrahamson, Magnus and Kos, J},
  issn         = {1742-464X},
  keyword      = {antigen presentation,cystatin,inhibition,cathepsin,cysteine protease},
  language     = {eng},
  number       = {6},
  pages        = {1535--1545},
  publisher    = {Federation of European Neuroscience Societies and Blackwell Publishing Ltd},
  series       = {The FEBS Journal},
  title        = {Inhibitory properties of cystatin F and its localization in U937 promonocyte cells},
  url          = {http://dx.doi.org/10.1111/j.1742-4658.2005.04594.x},
  volume       = {272},
  year         = {2005},
}