Effects of DDB2 overexpression on UV toxicity and cell growth
| Autor: | Kui Yuan Peng, 彭奎元 |
|---|---|
| Rok vydání: | 2008 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 96 Damaged DNA-binding protein 2 (DDB2) is one subunit of heterodimeric DDB complex and functions as a recognition protein in early step of nucleotide excision repair of UV damage. Except the major role in DNA repair, DDB2 may involve in other functions such as transcriptional co-activator, cell cycle regulator, nuclear transporter, and tumor suppressor. Our lab investigated the role of DDB2 in cross-resistance of drug-resistant cell lines and found that DDB2 protects cells from UV-induced apoptosis. Moreover, DDB2 is able to induce cFLIP protein and protect cells from TNF signaling-mediated apoptosis. Here I studied the effects of DDB2 over-expression on UV-toxicity and cell growth in cisplatin-resistant cell lines (R18), in which the DDB2 level had been knocked-down by stable expression of antisense strand of DDB2 cDNA. The anti-apoptotic effect on UV-irradiation by DDB2 described before was not clearly seen in my hands. Neither the induction of cFLIP by DDB2 over-expression was seen by me. One possible reason is the highly endogenous DDB2 protein in R18, which may mask the protective effects. However, DDB2 over-expression in cells with low level or none DDB2/cFLIP (XPA, VA13) neither displayed the protection effect. Nevertheless, over-expression of DDB2 enhances cell growth in R18 compared to control cells. It suggests that DDB2 may involve in the control of cell growth. In investigation of cFLIP induced by DDB2 over-expression, I found an alternative cFLIP, whose molecular mass was only 2kD less than the deposited one. Analysis of cDNA sequence indicated a putative Kozak sequence located downstream of the deposited start site. It is interesting to explore whether the shorter cFLIP displays the same function as the deposited one. To answer it, the shorter cFLIP is cloned and the biological function can be studied further. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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