The transcription factor C/EBP α controls the role of cystatin F during the differentiation of monocytes to macrophages

Dautović, Esmeralda; Nanut, Milica Perišić; Softić, Adaleta; Kos, Janko

doi:10.1016/j.ejcb.2018.07.002

Cited by 16 publications

(13 citation statements)

References 37 publications

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“…Changes in cystatin F levels following stimulation have been reported and were dependent on cell type and stimulation agents. Similarly to our findings, the differentiation of U937 and HL-60 cells with PMA caused a decrease in dimeric and monomeric forms of cystatin F 11, 36. On the other hand, in monocyte-derived dendritic cells stimulated with toll-like receptor 3 ligand (polyinosinic:polycytidylic acid) or toll-like receptor 4 ligand (lipopolysaccharide), cystatin F levels were increased 18.…”

Section: Discussionsupporting

confidence: 89%

“…In immune cells a notable role is attributed to cystatin F, a tight-binding inhibitor of cysteine cathepsins and legumain, which has several features distinguishing it from other members of cystatins II family. First, it is synthesised predominantly in immune cells and its expression depends on their activation state or differentiation status 11, 12, 13, 14. Secondly, it presents as a dimer, stabilized by disulphide bonds15 and as a dimer it does not inhibit cysteine cathepsins 16, 17.…”

Section: Introductionmentioning

confidence: 99%

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Increased cystatin F levels correlate with decreased cytotoxicity of cytotoxic T cells

Prunk

Nanut

Sabotič

et al. 2019

Radiology and Oncology

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BackgroundCystatin F is a protein inhibitor of cysteine peptidases, expressed predominantly in immune cells and localised in endosomal/lysosomal compartments. In cytotoxic immune cells cystatin F inhibits both the major pro-granzyme convertases, cathepsins C and H that activate granzymes, and cathepsin L, that acts as perforin activator. Since perforin and granzymes are crucial molecules for target cell killing by cytotoxic lymphocytes, defects in the activation of either granzymes or perforin can affect their cytotoxic potential.Materials and methodsLevels of cystatin F were assessed by western blot and interactions of cystatin F with cathepsins C, H and L were analysed by immunoprecipitation and confocal microscopy. In TALL-104 cells specific activities of the cathepsins and granzyme B were determined using peptide substrates.ResultsTwo models of reduced T cell cytotoxicity of TALL-104 cell line were established, either by treatment by ionomycin or by immunosuppressive transforming growth factor beta. Reduced cytotoxicity correlated with increased levels of cystatin F and with attenuated activities of cathepsins C, H and L and of granzyme B. Co-localisation of cystatin F and cathepsins C, H and L and interactions between cystatin F and cathepsins C and H were demonstrated.ConclusionsCystatin F is designated as a possible regulator of T cell cytotoxicity, similar to its role in natural killer cells.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Increased cystatin F levels correlate with decreased cytotoxicity of cytotoxic T cells

Prunk

Nanut

Sabotič

et al. 2019

Radiology and Oncology

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“…In the saliva, we found that cathepsin-G and cystatin-F were specifically accumulated in LTBI patients. Cathepsin-G is an antibacterial protein with activity against Gram-negative bacteria (53), and cystatin-F has been recently identified as a key factor in the differentiation process from monocytes to macrophages (54,55).…”

Section: Specific Proteomic Signature Of Ltbi Patientsmentioning

confidence: 99%

High-resolution quantitative proteomics applied to the study of the specific protein signature in the sputum and saliva of active tuberculosis patients and their infected and uninfected contacts

Mateos

Estévez

González-Fernández

et al. 2019

Journal of Proteomics

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“…Moreover, expression of CST7 has been observed in various human cancer cell lines established from malignant tumors. As the only family 2 cystatin able to enter endosomal/lysosomal vesicles and to regulate directly the activity of intracellular cysteine cathepsins, CST7 is highly upregulated in promonocytic U937 and promyeloblast HL-60 cells (26). Pierre and Mellman (37) reported that the apparent distribution of smaller vesicles/particles in U937 cells indicates that CST7 is partially localized to organelles that resemble fusion lysosomes/endosomes, wherein antigen and constant chain processing occurs in antigen-presenting cells.…”

Section: Discussionmentioning

confidence: 99%

Cystatin F as a key family 2 cystatin subunit and prognostic biomarker for early‑stage pancreatic ductal adenocarcinoma

Yang

Liu

et al. 2019

Oncol Rep

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Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, and early diagnosis and assessment may enhance the quality of life and survival of patients. The prognostic value of key family 2 cystatins subunit in PDAC patients remains unknown. The potential molecular roles of family 2 cystatins and related pathways were investigated using bioinformatics analysis. The relationship of family 2 cystatin expression levels and clinical outcomes of 112 patients with early-stage PDAC were evaluated via univariate and combined survival analysis. A prognostic nomogram model was also constructed and gene set enrichment analysis was performed to investigate potential pathways in PDAC. The pathways, interaction networks, and Gene Ontology term analysis of the cystatin gene family were analyzed in the present study. Cystatin F (CST7) was identified as the key subunit of family 2 cystatins in survival analysis. PDAC patients who harbored a higher expression level of CST7 had a lower risk in overall survival (adjusted HR OS =0.44, 95% CI=0.25-0.77, P=0.004) and a longer survival time in various subgroups. The prognostic nomogram indicated that the CST7 expression model effectively predicted the outcomes of patients with early-stage PDAC (predictive ability >0.75). In the gene set enrichment analysis, it was revealed that CST7 expression may be involved in immune regulation and be associated with cell adhesion. CST7 could be a useful biomarker for the prognostic prediction of early-stage PDAC after pancreaticoduodenectomy.

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The transcription factor C/EBP α controls the role of cystatin F during the differentiation of monocytes to macrophages

Cited by 16 publications

References 37 publications

Increased cystatin F levels correlate with decreased cytotoxicity of cytotoxic T cells

Increased cystatin F levels correlate with decreased cytotoxicity of cytotoxic T cells

High-resolution quantitative proteomics applied to the study of the specific protein signature in the sputum and saliva of active tuberculosis patients and their infected and uninfected contacts

Cystatin F as a key family 2 cystatin subunit and prognostic biomarker for early‑stage pancreatic ductal adenocarcinoma

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