| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1999: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Research Abstract |
We cloned a novel Kruppel-type zinc finger gene, ZK1, induced following exposure to ionizing radiation (Biochem. Biophys. Res. Commun. 249 : 595-600, 1998.) ZK1 enhances apoptotic death on hematopoietic cells after exposure to ionizing radiation.
We investigated function of the ZK1 gene product on apoptotic death caused by various stresses such as anti-tumor drugs, VP-16 or cisplatin, heat shock, or H_2O_2 on other cell types such as squamous or adenomatous carcinoma cells
To elucidate this function of the ZK1 gene product, we constructed HeLa, MCAS (adenomatous cell type), SCC-TF (squamous cell type), and U937 (leukemia cell type) stably transfected with ZK1cDNA in expression vector, pBK-CMV.These transfectants had higher sensitivity to exposure not only to ionizing radiation but also to anti-tumor drugs, heat shock (42℃) or H_2O_2. These data suggest that ZK1 has some functions on common parts lying signalling pathway of apoptotic cell death caused by various stresses.
We further analyzed binding sequence on genomic DNA of the ZK1 gene product by PCR and EMSA techniques. As the result of this research, we found that the ZK1 gene product could bind CACCC motif.
This result strongly suggest that the ZK1 gene product can function as a transcriptional regulator. Further analysis will be needed to elucidate target genes lying signalling pathway of apoptotic cell death transcriptionally regulated by the ZK1 gene product.
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