| title: | THE ROLE OF ARF IN CELLULAR RESPONSE TO DNA DAMAGE AND GENOME DESTABILIZATION |
|---|---|
| reg no: | ETF5801 |
| project type: | Estonian Science Foundation research grant |
| subject: |
1.8. Molecular Biology 3.1. Basic Medicine |
| status: | accepted |
| institution: | TU Faculty of Biology and Geography |
| head of project: | Dina Lepik |
| duration: | 01.01.2004 - 31.12.2007 |
| description: | The status of p53 in the cells as the basic factor determining the response of cells to external stress signals has been overestimated. By now it is clear that more important is the functionality of p53, that is greatly regulated by other cellular proteins, that could transduce the signal either to p53 or bypass it completely, having their own alternative effect. Besides p53 there are other tumor suppressors also having critical importance in the prevention of tumors and in keeping the intactness of the genome. One of the most important such proteins is ARF. The aim of the current project is to study the role of ARF in cellular transformation and in the response of cells to DNA damage, caused by UV or a chemical agent campthotecin, also in the destabilization of the genome brought along by polyomavirus replication. ARF like p53 can be called a tumor suppressor gene, the presence of which is essential for the prevention of tumors. Consequently this study should help to broaden our understanding of the mechanisms of tumor development. Besides it would set light to the functioning of tumor suppressor genes and other mechanisms responsible for the prevention of transformation and malignant growth in normal cells More specific aims of the project are the following: 1) To show if p19ARF has p53-independent functions in MEFs 2) To determine the role of p19ARF in the case of DNA damage 3) To create a Tet inducible ARF expressing cell line on the basis of ARF-/-MEFs 4) To study the role of p19ARF in the regulation of p53 target genes 5) To study the role of ARF in the response of cells to polyomavirus infection at the same time using the Py system for studying the interplay and signal transduction between ARF/Mdm2/p53 and pRb/E2F1 pathways. For that purpose we want to study: a) The effect of Py T antigens on ARF and p53; b) The effect of Py replication on p53. 6) To study possible prosttranslational modifications induced by ARF in the p53 protein. |
| project group | ||||
|---|---|---|---|---|
| no | name | institution | position | |
| 1. | Lilian Kadaja-Saarepuu | TÜMRI | teadur | |
| 2. | Dina Lepik | TU Faculty of Biology and Geography | senior scientist | |
| 3. | Anu Sikut | TÜMRI | assistent | |