Projects / Programmes
Proteomic identification of extracellular substrates of cysteine proteases
| Code |
Science |
Field |
Subfield |
| 1.05.00 |
Natural sciences and mathematics |
Biochemistry and molecular biology |
|
| Code |
Science |
Field |
| P004 |
Natural sciences and mathematics |
Biochemistry, Metabolism |
proteomics, proteolysis, cathepsin, cancer, substrate, invasion, immunohistochemistry
Researchers (4)
| no. |
Code |
Name and surname |
Research area |
Role |
Period |
No. of publicationsNo. of publications |
| 1. |
23573 |
PhD Dejan Caglič |
Biochemistry and molecular biology |
Researcher |
2008 - 2011 |
0 |
| 2. |
18801 |
PhD Marko Fonović |
Biochemistry and molecular biology |
Head |
2008 - 2011 |
0 |
| 3. |
07561 |
PhD Boris Turk |
Biochemistry and molecular biology |
Researcher |
2008 - 2011 |
0 |
| 4. |
21619 |
PhD Olga Vasiljeva |
Oncology |
Researcher |
2008 - 2011 |
0 |
Organisations (1)
| no. |
Code |
Research organisation |
City |
Registration number |
No. of publicationsNo. of publications |
| 1. |
0106 |
Jožef Stefan Institute |
Ljubljana |
5051606000 |
18 |
Abstract
Proteases play a crucial role in cell surface signaling pathways and extracellular matrix remodeling. Cell surface proteins can be activated, inactivated or can undergo other changes in their function upon proteolysis. Cysteine cathepsins are a group of papain-like cysteine proteases which are mainly located within the lysosomes. However, in various types of cancer, they are transported to outer cellular membrane and extracellular space. There they cleave membrane proteins and extracellular matrix and promote various stages of tumor progression. Tumor microenvironment is composed of normal epithelial cells, tumor cells and immune cells and they all provide proteases and their substrates that promote cancer progression. Only a few extracellular cathepsin protein substrates have been identified to date and since no global proteomic search has been reported yet, majority of them still need to be identified. Aim of our work is to use mass spectrometry for identification of membrane proteins which can be cleaved by cathepsins and to verify physiological relevance of this degradation on cellular and animal models. Identification of cathepsin substrates in complex biological samples will give an important insight in our understanding of cathepsin physiological functions and their role in cancer progression.
Significance for science
Cathepsins have been identified as important players in the process of cancer progression. They are known to promote invasion, proliferaton, apoptosis and angiogenesis. Despite that, their exact mode of action on molecular level still remains largely unknown. Research performed within this project was the first large scale proteomic identification of extracellular cathepsin substrates. Identification of those substrates and their validation on cellular and animal models will provide a better understanding of cathepsin physiological function and especially their role in tumor progression. Results obtained in this project have opened numerous possibilities for further competitive research in the field of cancerogenesis. Obtained results will also promote other cancer related projects within our department and could open the way toward new approaches in cancer treatment.
Proteomics has became an indispensible tool for advancement of biomedical research in the modern world and without this know-how, Slovenian research would start lagging behind. While working on this project we have expanded our experience in proteomic analysis. We have introduced methodologies which are completely novel in slovenian research community. With this experience, we will be able to introduce proteomics technology to Slovenian research community. This advancement will be beneficial for the quality of all biomedical and biological research in Slovenia.
Significance for the country
Being the first proteomic laboratory in the country, our services and know-how is also available to other research and development oriented institutions and companies in Slovenia. Proteomics is important part of basic biological and medical research but it is even more crucial in modern pharmaceutical industry. Production of recombinant drugs requires the exact knowledge of the protein sequence and its posttranslational modifications. This can only be achieved through proteomic analysis. While working on this project, we have expanded our experimental knowledge and introduced new methodologies in our workflow. This will enable us to provide better service to other Slovenian research institutions and it will also further our collaborations with pharmaceutical and biotech industry. By proteomics, our department has also established beneficial collaborations with industrial partners through Centre of excellence CIPKEBIP and Centre of competence Brin.
We are confident, that research results obtained from this project will have significant impact in the field of cancer research and will promote Slovenian science through many international research conference participations and publications in high impact scientific journals. They have also tighten our connections with some of the worlds top research institutions. Those connections will increase our possibilities for participation in leading international research projects and will keep Slovenia in touch with worlds cutting edge science.
Most important scientific results
Annual report
2008,
2009,
final report,
complete report on dLib.si
Most important socioeconomically and culturally relevant results
Annual report
2008,
2009,
final report,
complete report on dLib.si
