Inhibitory properties of cystatin F and its localization in U937 promonocyte cells
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/250549
- author
- Langerholc, T ; Zavasnik-Bergant, V ; Turk, B ; Turk, V ; Abrahamson, Magnus LU and Kos, J
- organization
- publishing date
- 2005
- 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
- Wiley-Blackwell
- 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
- 2016-04-01 16:36:10
- date last changed
- 2022-01-28 20:50:27
@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}},
keywords = {{antigen presentation; cystatin; inhibition; cathepsin; cysteine protease}},
language = {{eng}},
number = {{6}},
pages = {{1535--1545}},
publisher = {{Wiley-Blackwell}},
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}},
doi = {{10.1111/j.1742-4658.2005.04594.x}},
volume = {{272}},
year = {{2005}},
}