Cystatin F regulates proteinase activity in IL-2-activated natural killer cells

Katarina Maher, Spela Konjar, Colin Watts, Boris Turk, Natasa Kopitar-Jerala (Lead / Corresponding author)

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Cystatin F is a unique member of the cystatin family of cysteine protease inhibitors, which is synthesized as an inactive dimer and it is activated by N-terminal cleavage in the endolysosomes. It is expressed in the cells of the immune system: myeloid cells and the cells involved in target cell killing: natural killer (NK) cells and cytotoxic T cells (CTLs). Upon activation of the NK cells with interleukin 2 (IL-2), cystatin F was found upregulated and co-localized in cytotoxic granules with cathepsin C (CatC) and CatV. However, cystatin F inhibits the CatC in cells only when its N-terminal part is processed. Although cystatin F could inhibit both CatV and CatC, the IL-2 stimulation of the YT cells resulted in an increased CatV activity, while the CatC activity was unchanged. The incubation of IL-2 activated NK cells with a cysteine proteinase inhibitor E-64d increased the cystatin F dimer formation. Our results suggest that cystatin F not only inhibits CatV, but it is processed by the CatV in order to inhibit the CatC activity in cytotoxic granules. The regulation of the CatC activity in the cytotoxic granules of the NK cells by the cystatin F could be important for the processing and activation of granule-associated serine proteases - granzymes.
Original languageEnglish
Pages (from-to)957-965
Number of pages9
JournalProtein and Peptide Letters
Volume21
Issue number9
DOIs
Publication statusPublished - 2014

Fingerprint Dive into the research topics of 'Cystatin F regulates proteinase activity in IL-2-activated natural killer cells'. Together they form a unique fingerprint.

  • Profiles

    No photo of Colin Watts

    Cite this