| Budget Amount *help |
¥10,000,000 (Direct Cost: ¥10,000,000)
Fiscal Year 1999: ¥10,000,000 (Direct Cost: ¥10,000,000)
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| Research Abstract |
A novel myeloid leukemia gene, Evi9, has been isolated from the common retroviral integration site of BXH-2 mouse leukemia. The functional analysis of the Evi9 protein was carried out, and the human homologue of Evi9 was identified. The followings were clarified in this year.
(l) The Evi9 gene encodes a zinc finger protein, and three protein isoforms are produced by alternative splicing. The isoforms that have a double zinc finger as well as an acidic domain are located in the nucleus, whereas the other isoform that lacks both domains are in the cytoplasm. It has been shown that Evi9 colocalizes with BCL6 in the nucleus, and we clarified that the double zinc finger of Evi9 and the POZ domain of BCL6 physically interact with each another.
(2) The expression of Evi9 was downregulated during myeloid differentiation of the HL60 cell induced by retinoic acid. Moreover, induction of Evi9 blocked myeloid differentiation of the HL60 cell, and also it inhibited apoptosis during differentiation. On the other hand, when HL60 and U937 cells were differentiated toward the monocyte by TPA, Evi9 was transiently downregtulated and then it showed upregulated expression. We are currently investigating the role of Evi9 in monocytic differentiation.
(3) Since it was suggested that the Evi9 protein functions as a transcriptional regtulator, the transcriptional activity of Evi9 was examined using GAL4 fusion proteins. Evi9 acts as the transcriptional repressor, and there is a repression domain in the zinc figer region.
(4) The human EVI9 gene was shown to be located at chromosome 2p13 by FISH.As some cases of human malignant lymphoma have shown the abnormalites in this region, we are currently investigating the possible EVI9 involvement in malignant lymphoma.
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