Cystatin F as a regulator of immune cell cytotoxicity

Cancer Immunology, Immunotherapy : CII
Janko KosAnahid Jewett

Abstract

Cysteine cathepsins are lysosomal peptidases involved in the regulation of innate and adaptive immune responses. Among the diverse processes, regulation of granule-dependent cytotoxicity of cytotoxic T-lymphocytes (CTLs) and natural killer (NK) cells during cancer progression has recently gained significant attention. The function of cysteine cathepsins is regulated by endogenous cysteine protease inhibitors-cystatins. Whereas other cystatins are generally cytosolic or extracellular proteins, cystatin F is present in endosomes and lysosomes and is thus able to regulate the activity of its target directly. It is delivered to endosomal/lysosomal vesicles as an inactive, disulphide-linked dimer. Proteolytic cleavage of its N-terminal part leads to the monomer, the only form that is a potent inhibitor of cathepsins C, H and L, involved in the activation of granzymes and perforin. In NK cells and CTLs the levels of active cathepsin C and of granzyme B are dependent on the concentration of monomeric, active cystatin F. In tumour microenvironment, inactive dimeric cystatin F can be secreted from tumour cells or immune cells and further taken up by the cytotoxic cells. Subsequent monomerization and inhibition of cysteine cathepsins wit...Continue Reading

References

Feb 1, 1995·Oral Microbiology and Immunology·M GuE J Bergey
Apr 9, 1998·Biochimica Et Biophysica Acta·L J PageG M Griffiths
Jun 20, 1998·The Journal of Biological Chemistry·S HalfonG Zurawski
Sep 12, 1998·The Journal of Biological Chemistry·J NiM Abrahamson
Jun 26, 1999·The Journal of Biological Chemistry·M Alvarez-FernandezM Abrahamson
Sep 5, 2001·The EMBO Journal·V TurkD Turk
Oct 3, 2002·International Immunology·Aya Obata-OnaiKouji Mathushima
Oct 3, 2002·Nature Reviews. Immunology·Joseph A Trapani, Mark J Smyth
Nov 9, 2002·European Journal of Biochemistry·Carl-Michael NathansonMagnus Abrahamson
Jun 24, 2003·Biochimica Et Biophysica Acta·Kensaku OhashiEmiko Sano
Nov 11, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Dima El-SukkariJosé A Villadangos
Dec 9, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Christine T N PhamTimothy J Ley
Feb 25, 2005·The Journal of Biological Chemistry·Marcia Alvarez-FernandezXiao-Dong Su
Mar 9, 2005·The FEBS Journal·Tomaz LangerholcJanko Kos
Jan 19, 2006·The Journal of Investigative Dermatology·Mads Hald AndersenJürgen C Becker
Oct 27, 2006·The Journal of Biological Chemistry·Annette M LechnerDorit K Nägler
Feb 8, 2008·The EMBO Journal·Garth HamiltonColin Watts
Feb 29, 2008·Annual Review of Immunology·Dipanjan Chowdhury, Judy Lieberman
May 30, 2008·Frontiers in Bioscience : a Journal and Virtual Library·Tina Zavasnik-Bergant
Jul 16, 2008·Methods : a Companion to Methods in Enzymology·Ola SöderbergUlf Landegren
Jul 31, 2008·Journal of Cell Science·Zala JevnikarJanko Kos
Aug 15, 2008·Journal of Leukocyte Biology·Natasa ObermajerJanko Kos
Dec 25, 2008·Proceedings of the National Academy of Sciences of the United States of America·Chi-Bun ChanKeqiang Ye
Jul 29, 2009·European Journal of Immunology·Jeff D ColbertColin Watts
Nov 26, 2009·Nature Reviews. Immunology·Phillip I BirdJosé A Villadangos
May 4, 2010·The Journal of Biological Chemistry·Michael E D'AngeloVivien R Sutton
Mar 1, 2012·European Journal of Cell Biology·Spela MagisterJanko Kos
Mar 1, 2012·The EMBO Journal·Boris TurkVito Turk
Sep 11, 2012·Archives of Medical Research·Luis M TeranThomas Franz
Oct 26, 2013·Nucleic Acids Research·Neil D RawlingsAlex Bateman
Apr 8, 2014·Protein and Peptide Letters·Katarina MaherNatasa Kopitar-Jerala

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Citations

Mar 7, 2019·Radiology and Oncology·Mateja PrunkJanko Kos
Apr 30, 2020·Journal for Immunotherapy of Cancer·Kristen SolocinskiJames W Hodge
Sep 27, 2019·Frontiers in Immunology·Tanja JakošJanko Kos
May 3, 2019·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Thomas D Lockwood
Feb 13, 2021·Frontiers in Cellular Neuroscience·Annapoorani MuthiahDominik Fröhlich
Jun 17, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Sara H McDowellChristopher J Scott

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