Janko Kos

University of Ljubljana

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Co-Authors

Vito Türk

Jožef Stefan Institute

I. Harapin

University of Zagreb

Anja Pišlar

University of Ljubljana

Stanislav Gobec

University of Ljubljana

Jerica Sabotič

Jožef Stefan Institute

Nataša Obermajer

University of Pittsburgh

Ana Mitrović

University of Ljubljana

Tamara T. Lah

National Institute of Biology

Milica Perišić Nanut

Jožef Stefan International Postgraduate School

Zala Jevnikar

AstraZeneca (Sweden)

Cooperative Institutions

University of Ljubljana

242

Institut za filozofiju

123

Jožef Stefan Institute

120

Schneeberger (Switzerland)

106

University of Zagreb

Jožef Stefan International Postgraduate School

Ljubljana University Medical Centre

National Institute of Biology

Centre National de la Recherche Scientifique

University of California, Los Angeles

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Three‐dimensional invasion of macrophages is mediated by cysteine cathepsins in protrusive podosomes

European Journal of Immunology (2012)

Zala Jevnikar Bojana Mirković Urša Pečar Fonović Nace Zidar Urban Švajger

Podosomes, specialized actin‐rich structures in macrophages (Mfs), degrade the extra‐cellular matrix (ECM) and are involved in cell migration. On two‐dimensional (2D) surfaces Mfs form spot‐like podosomes at the ventral cell surface that develop into protrusive structures in a three‐dimensional (3D) environment resembling the ECM. We have shown that the tips of these protrusive podosomes are characterized by increased accumulation of cysteine cathepsins (Cts) B, X, S, H, and L, both in human blood Mfs and in human monocytic cell line U‐937. Monocyte‐to‐Mf differentiation induces an increase in cysteine cathepsin expression and activity, promoting their translocation to the cell surface, where they interact with ECM. This group of proteases is crucial for the extracellular as well as intracellular degradation of ECM, as demonstrated by quantitative monitoring of collagen IV degradation. Furthermore, inhibiting CtsB, X, and S significantly impairs Mf invasion through the 3D matrix. Time‐lapse live‐cell imaging of CtsB activity revealed that the extracellular and the intracellular ECM degradation are associated with extensive endocytosis at the tip of protrusive podosomes. The targeting of cysteine cathepsins, as the major mediators of human Mf 3D invasion, could be an approach to the treatment of inflammatory and cancerous diseases.

Podosome

Invadopodia

10.1002/eji.201242610

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Citations (35)

Trypsin-specific Inhibitors from the Macrolepiota procera, Armillaria mellea and Amanita phalloides wild mushrooms.

Acta Biochimica Polonica (1970)

Tjaša Lukanc Jože Brzin Janko Kos Jerica Sabotič

Wild growing mushrooms are a rich source of novel proteins with unique features. We have isolated and characterized trypsin inhibitors from two edible mushrooms, the honey fungus (Armillaria mellea) and the parasol mushroom (Macrolepiota procera), and from the poisonous death cap (Amanita phalloides). The trypsin inhibitors isolated: armespin, macrospin and amphaspin, have similar molecular masses, acidic isoelectric points and are not N-glycosylated. They are very strong trypsin inhibitors and weak chymotrypsin inhibitors. They are resistant to exposure to high temperatures and withstand extreme pH values. These exceptional characteristics are advantageous for their potential use in biotechnology, agriculture and medicine.

Armillaria mellea

Amanita phalloides

Edible mushroom

10.18388/abp.2015_1187

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Citations (5)

NK cells shape pancreatic and oral tumor microenvironments; role in inhibition of tumor growth and metastasis

Seminars in Cancer Biology (2018)

Anahid Jewett Janko Kos Yuman Fong Meng-Wei Ko Tahmineh Safaei

Adoptive Cell Transfer

NK-92

10.1016/j.semcancer.2018.08.001

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Citations (59)

Cathepsin B and its inhibitor stefin A in brain tumors

Pflügers Archiv - European Journal of Physiology (2000)

Tadej Strojnik Irena Zajc Aleš Bervar Boris Židanik Rastko Golouh

10.1007/s004240000114

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Citations (37)

CNL–Clitocybe nebularis Lectin—The Fungal GalNAcβ1-4GlcNAc-Binding Lectin

Molecules (2019)

Jerica Sabotič Janko Kos

Clitocybe nebularis lectin (CNL) is present in fruiting bodies of clouded agaric along with several similar isolectins that are all small and stable proteins. It is a beta-trefoil type lectin forming homodimers that are essential for its functionality. It binds specifically N,N'-diacetyllactosediamine (GalNAcβ1-4GlcNAc, LacDiNac) and human blood group A determinant-containing glycan epitopes. Its most probable function is to defend fruiting bodies against predators and parasites. In addition, an endogenous regulatory function is possible for CNL, as indicated by its interaction with fungal protease inhibitors sharing the beta-trefoil fold. CNL is toxic to insects, nematodes and amoebae, as well as to leukemic T-cell lines. Bivalent carbohydrate binding is essential for the toxicity of CNL, against both invertebrates and cancer-derived cell lines. In addition, CNL exhibits potent immunostimulation of human dendritic cells, resulting in a strong T helper cell type 1 response. Based on its unique characteristics, CNL is a promising candidate for applications in human and veterinary medicine as well as in agriculture, for plant protection.

C-type lectin

10.3390/molecules24234204

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Citations (9)

The role of cysteine peptidases in coronavirus cell entry and replication: The therapeutic potential of cathepsin inhibitors

PLoS Pathogens (2020)

Anja Pišlar Ana Mitrović Jerica Sabotič Urša Pečar Fonović Milica Perišić Nanut

Over the last 2 decades, several coronaviruses (CoVs) have crossed the species barrier into humans, causing highly prevalent and severe respiratory diseases, often with fatal outcomes. CoVs are a large group of enveloped, single-stranded, positive-sense RNA viruses, which encode large replicase polyproteins that are processed by viral peptidases to generate the nonstructural proteins (Nsps) that mediate viral RNA synthesis. Papain-like peptidases (PLPs) and chymotrypsin-like cysteine 3C-like peptidase are essential for coronaviral replication and represent attractive antiviral drug targets. Furthermore, CoVs utilize the activation of their envelope spike glycoproteins by host cell peptidases to gain entry into cells. CoVs have evolved multiple strategies for spike protein activation, including the utilization of lysosomal cysteine cathepsins. In this review, viral and host peptidases involved in CoV cell entry and replication are discussed in depth, with an emphasis on papain-like cysteine cathepsins. Furthermore, important findings on cysteine peptidase inhibitors with regard to virus attenuation are highlighted as well as the potential of such inhibitors for future treatment strategies for CoV-related diseases.

Polyproteins

Cathepsin L

Coronavirus

10.1371/journal.ppat.1009013

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Citations (103)

A field outbreak of aflatoxicosis with high fatality rate in feedlot calves in Tehran Province - Iran.

Mohammad Tooloei Nadalian M.Gh.Alireza Khosravi Javad Ashrafi Helan R. Najafie

Feedlot

Attack rate

Case fatality rate

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The expression of lysosomal proteinases and their inhibitors in breast cancer: Possible relationship to prognosis of the disease

Pathology & Oncology Research (1997)

Tamara T. Lah Janko Kos Andrej Blejec Snežana FrkoviČ-Georgio Rastko Golouh

Cathepsin L

Proteolysis

Proteolytic enzymes

10.1007/bf02907801

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Citations (54)

Cysteine proteinase inhibitors stefin A, stefin B, and cystatin C in sera from patients with colorectal cancer: relation to prognosis.

PubMed (2000)

Janko Kos Marta Krašovec Nina Cimerman Hans Jørgen Nielsen Ib Jarle Christensen

The levels of cysteine proteinase inhibitors stefin A, stefin B, and cystatin C were determined using ELISAs in sera obtained preoperatively from 345 patients with colorectal cancer and in control sera from 125 healthy blood donors. The levels of stefin A and cystatin C were found to be moderately increased in patient sera (1.4-fold and 1.6-fold, respectively; P < 0.0001), whereas the level of stefin B remained statistically unchanged when compared with controls. The medians were 4.3 ng/ml versus 3.2 ng/ml for stefin A, 1.2 ng/ml versus 1.7 ng/ml for stefin B, and 679 ng/ml versus 425 ng/ml for cystatin C. In patient sera, a weak correlation of cystatin C with age (r = 0.34; P < 0.001) and gender (P = 0.01) was found. Stefin A and cystatin C levels were independent of Dukes' stage, whereas stefin B correlated significantly with Dukes' stage, its level being the highest in stage D (P < 0.007). Stefin B and cystatin C correlated with survival, whereas stefin A was not a significant prognostic factor in this study. Using medians as cutoff values, patients with high levels of stefin B and patients with high levels of cystatin C exhibited a significantly higher risk of death than those with low levels of inhibitors (hazard ratio = 1.6; 95% confidence interval, 1.2-2.2; P = 0.002 for stefin B; hazard ratio = 1.3; 95% confidence interval, 1.0-1.8; P = 0.04 for cystatin C). Our results reveal a correlation between high levels of extracellular cysteine proteinase inhibitors and short survival in patients with colorectal cancer, and the data thus support previous studies suggesting a contributing role of protease inhibitors in the progression of cancer.

Cystatin

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Citations (183)

The survey on prevalence of E. coli O157:H7 using VT1, 2 and eae genes from sheep in Shiraz-Iran.

Yahya Tahamtan S. S. Shekarforoosh S A Pourbakhsh I. Harapin Janko Kos

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