| title: | About the cross-talk between CD43- and p53-mediated signaling pathways |
|---|---|
| reg no: | ETF6459 |
| project type: | Estonian Science Foundation research grant |
| status: | accepted |
| institution: | University of Tartu |
| head of project: | Toivo Maimets |
| duration: | 01.01.2005 - 31.12.2008 |
| description: | CD43 is a transmembrane sialylated glycoprotein expressed on the surface of most hematopoietic cells, where it is believed to have a role both in cell adhesion and signal transduction. CD43 has been considered to be specific to hematopoietic cells, but later it has been shown that CD43 is a frequent event in tumors of non-hematopoietic origin, but not in normal tissue. CD43 expression is also frequent in established human cell lines of different origins. This suggests that CD43 may have a role in tumor development. The accumulation of the p53 protein has been shown in early stages of different tumors including colon adenomas, but p53 mutations occur relatively late during colorectal carcinogenesis. The p53 protein accumulates in response to cell stress (DNA damage, uncontrolled proliferation, etc.), which results in cell cycle arrest or programmed cell death dependent on the extent of the stress. As the expression of CD43 in colon adenomas has been suggested to be also an early event, it was considered of interest to determine whether there was a crosstalk between the presence of CD43 and the p53-response pathway in early tumor development. We found that the overexpression of CD43 induces the accumulation of the p53 protein, which is dependent on tumor-suppressor protein ARF. It has also been shown that the cytoplasmic tail of CD43 interacts with β-catenin, which is an oncogene that promotes the cell survival and also has been shown to induce the accumulation of the p53 protein. The exact mechanism, how CD43 induces the p53-response pathways remains unclear. This therefore needs further investigation and make up the goals of the present grant application: (1) to investigate the correlation between the CD43 expression and the status of tumor suppressor proteins p53 and ARF in human tumors, (2) to find out whether CD43 has a influence on cell growth of non-hematopoietic cells, (3) to study the role of CD43 in apoptosis inhibition, (4) to study the crosstalk between CD43-mediated and p53-dependent signaling pathways. |
| project group | ||||
|---|---|---|---|---|
| no | name | institution | position | |
| 1. | Jaak Jänes | University of Tartu | Ph D student | |
| 2. | Lilian Kadaja-Saarepuu | University of Tartu | research scientist | |
| 3. | Sirle Laos | University of Tartu | Ph.D student | |
| 4. | Dina Lepik | University of Tartu | senior scientist | |
| 5. | Toivo Maimets | University of Tartu | Professor | |