1999 Fiscal Year Final Research Report Summary
Functional analysis of DAN and DA41 proteins in early embryogenesis
| Project/Area Number |
10680658
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Molecular biology
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| Research Institution | Chiba Cancer Center Research Institute |
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Principal Investigator |
OZAKI Toshinori Chiba Cancer Center Research Institute, 研究局・生化学研究部, 研究員 (40260252)
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| Project Period (FY) |
1998 – 1999
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| Keywords | BMP4 / DA41 / DAN / Growth suppression |
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| Research Abstract |
(A) Functional analysis of DAN
Northern blot analysis revealed that the expression of DAN was significantly down-regulated in human osteosarcoma cell line SAOS-2. Overexpression of DAN in SAOS-2 resulted in a massive growth suppression as demonstrated by colony formation assays. N-terminal truncated form of DAN did not exhibit the growth suppressive activity, indicating that the secreted form of DAN is active. Reporter gene assay demonstrated that DAN inhibited the BMP4 signaling in mouse embryonic carcinoma P19 cells. These observations suggest that DAN, as well as Cerberus and Gremlin, may function as an antagonist against BMP in fog embryos and mammalian cells.
(B) Characterization of DA41
Ectopic overexpression of rat DA41 in V-Ha-ras-transformed 3Y1 cells (ras-3Y1) resulted in a significant growth suppression, which was associated with a remarkable reduction of CDK2 activity. Fluorescence in situ hybridization revealed that DA41 was mapped to human chromosome 9q21.2-q21.3, a position overlapping the candidate tumor suppressor locus for bladder cancer. Data base search for DA41-related proteins(s) identified mouse PLIC-1, PLIC-2, frog XDRP1, and yeast DSK2. It has been shown that XDRP1 inhibited the degradation of cyclin A and blocked the cell division. These observations suggest that DA41 and XDRP1 could share the similar function in the cell cycle regulation.
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