| Project/Area Number |
15300120
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Hokkaido University |
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Principal Investigator |
MATSUOKA Ichiro Hokkaido University, Graduate School of Pharmaceutical Sciences, Assoc.Prof., 大学院・薬学研究科, 助教授 (40157269)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUMOTO Ken-ichi Hokkaido University, Graduate School of Pharmaceutical Sciences, Assoc.Prof., 大学院・薬学研究科, 助教授 (30202328)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥14,400,000 (Direct Cost: ¥14,400,000)
Fiscal Year 2005: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 2004: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 2003: ¥5,300,000 (Direct Cost: ¥5,300,000)
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| Keywords | bone morphogenetic protein / retinoic acid / neuronal differentiation / BRINP family / sympathetic neuron / suppression of cell proliferation / gene knockout / neural-specific genes |
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| Research Abstract |
One of the important characteristics that distinguish neuronal cells from other cell types is the lack of cell proliferation. Thus, cell proliferation machinery in neuronal cell is strictly inactivated. Deregulation of cell proliferation machinery in neuronal cells should lead to traumatic situations, such as tumors. The mechanism that suppresses proliferation of the neuronal cells has not been clarified so far. Recently, we identified a novel gene family, BRINP (BMP/RA-Inducible Neural specific Protein) that are specifically expressed in nervous system. BRINP family members are quite unique in that they posses no conserved protein motif. In this project research we analyzed the roles of BRINPs in neural development and pathogenic situations. All three BRINPs are predominantly expressed in terminally differentiated neuronal cells from developmental stage to adulthood in complementary as well as in alternating manner among different regions in the nervous system. We found that neuronal
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expression of BRINP1 gene is specifically regulated by neuron-restrictive silencing factor (NRSF/REST). We then found that in neuroectdermal tumor cells (Daoy cells), aberrant high activity of transcription factor (NRSF/REST) leads to loss BRINP1 expression. Over-expression analysis indicated that BRINPs suppress cell cycle progression at G1/S transition in non-tumorigenic cell types. Interestingly, when over-expressed in Daoy cells, BRINPs induce apoptosis during the course of cell cycle progression. These results suggest that BRINPs suppress cell division of terminally differentiated neurons and also function as novel tumor suppressors. On the other hand, in adult animals, the expression of BRINP1 is regulated by neural activity suggesting its role in learning and memory. So far we have established a strain of BRINP1-deficient hetero mice. Physiological roles of BRINP1 gene in the neural development and tumor suppression will be analyzed by using BRINP1-deficient homo mice shortly. Production of BRINP2- and BRINP3-deficient mice will be followed. Less
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