Projects / Programmes
Katepsin E: karakterizacija in biološka vloga (Slovene)
| Code |
Science |
Field |
Subfield |
| 1.05.00 |
Natural sciences and mathematics |
Biochemistry and molecular biology |
|
| Code |
Science |
Field |
| 1.07 |
Natural Sciences |
Other natural sciences |
Researchers (6)
| no. |
Code |
Name and surname |
Research area |
Role |
Period |
No. of publicationsNo. of publications |
| 1. |
00449 |
PhD Iztok Dolenc |
Biochemistry and molecular biology |
Researcher |
2009 - 2012 |
110 |
| 2. |
09091 |
PhD Vida Puizdar |
Biochemistry and molecular biology |
Technical associate |
2009 - 2012 |
55 |
| 3. |
21560 |
PhD Urška Repnik |
Microbiology and immunology |
Researcher |
2009 - 2011 |
149 |
| 4. |
28484 |
PhD Dejan Suban |
Animal production |
Junior researcher |
2009 - 2012 |
17 |
| 5. |
28485 |
PhD Aleš Špes |
Biochemistry and molecular biology |
Junior researcher |
2009 - 2012 |
24 |
| 6. |
01085 |
PhD Vito Turk |
Biochemistry and molecular biology |
Head |
2009 - 2012 |
1,490 |
Organisations (1)
| no. |
Code |
Research organisation |
City |
Registration number |
No. of publicationsNo. of publications |
| 1. |
0106 |
Jožef Stefan Institute |
Ljubljana |
5051606000 |
90,742 |
Significance for science
The main purpose of this project was to further clarify the biochemical properties of aspartic proteases cathepsins D and E in order to better understand their role under normal and pathological conditions. Although lysosomal cathepsin D was well characterized, only little is known about its physiological substrates and biological role. On the other hand, the non-lysosomal cathepsin E is less characterized protein and only in recent years began more intensive studies of this enzyme, due to its role in cancers of the gastrointestinal tract. The discovery of the splice variant of cathepsin E in adenocarcinoma also points out to the importance of this enzyme in cancer and perhaps other diseases. Despite published reports about the expression of recombinant cathepsin E, the yields were very low. On the other side, we were able to obtain the enzyme in larger quantities in the baculovirus expression system, which enables us to pursue this research further. The splice variant of cathepsin E was firstly expressed as a protein. We investigated the specificity of cathepsin D and E on different substrates and it was found that they differ in their specificity towards different substrates (lysozyme, cystatins, neuropeptides). Preliminary studies using proteomics also show that there are certain differences in their specificity. Cathepsin E splice variant does not show enzyme activity but reacts with the pentapeptide pepstatin, suggesting some possible biological role, perhaps in cancer. An important finding is that cathepsin E and cysteine protease cathepsin X colocalize in the endosomes. Our studies led to the discovery that activated cathepsin E activates procathepsin X to the active enzyme. Studies of cathepsins D and E in various cell lines induced by the lysosomotropic detergent LeuLeuOMe suggest that these enzymes do not have a significant role in apoptosis.
These results allow further investigation, particularly the role of cathepsin E and its splice variant in cancer. These studies has basic character (biochemistry, biology, medicine) and are ofinterdisciplinary nature, allowing in the near future the transfer of basic knowledge into clinics (translational research).
Significance for the country
Proteases are currently one of the major targets in the search for new therapeutics. Numerous experimental and clinical research studies suggested the use of protease inhibitors in cancer treatment. Thus, the results of the proposed project will have a major importance in the evaluation of aspartic cathepsins as possible therapeutic targets in cancer and other diseases. In addition, the project could enable the identification of new diagnostic markers and drug targets for cancer treatment, which is of potential commercial interest. Proposed research and further use of representative animal cancer models are therefore extremely valuable tools and of high value for the evaluation of compounds on the preclinical level, which should be interesting for the pharmaceutical companies including those in Slovenia and the possibility to establish spin-off companies. For this reason it is important to pursue this research further and this is one of the longterm goals of the project. This is also clear from the intense research being carried-out on this enzymes at the international level. Moreover, the development of new knowledge favors the increase of the level of Slovenian research and cooperation with other research groups worldwide.
Although the proposed research is of basic nature, has also applied components and can be classified as strategic basic research. The project leader extensively collaborated in the past with Slovenian industry (Lek, Krka) which resulted in a substantial amount of contract based research. In the last years, many researchers were employed in the Slovene industry (i.e. Novartis Lek in the production of recombinant proteins) and other research institutes and universities.
These studies offers great opportunity for students to be trained in the most advanced methods and areas, including proteomics, established more than year ago within the group at IJS and chemogenomics in cooperation with European and other foreign partners. This field has namely high international priority as it is of major importance in target identification and validation during drug development. Some team members have received wide international recognition (EMBO member and member of several foreign academies and member of SAZU) which is very important for the promotion of Slovenia and preservation of national identity of Slovenia. The researchers of this group are part of Centre of Excellence (CoE) CIPKeBiP, coordinated by our institute.
Most important scientific results
Annual report
2009,
2010,
2011,
final report,
complete report on dLib.si
Most important socioeconomically and culturally relevant results
Annual report
2009,
2010,
2011,
final report,
complete report on dLib.si
