| Project/Area Number |
08458253
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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 | Osaka University |
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Principal Investigator |
YOSHIKAWA Kazuaki Institute for Protein Research, Professor, たんぱく質研究所, 教授 (30094452)
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| Co-Investigator(Kenkyū-buntansha) |
UETSUKI Taichi Institute for Protein Research, Instructor, たんぱく質研究所, 助手 (20260309)
TANIURA Hideo Institute for Protein Research, Instructor, たんぱく質研究所, 助手 (80263325)
NIINOBE Michio Institute for Protein Research, Associate Professor, たんぱく質研究所, 助教授 (80135748)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥7,300,000 (Direct Cost: ¥7,300,000)
Fiscal Year 1997: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1996: ¥5,500,000 (Direct Cost: ¥5,500,000)
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| Keywords | Necdin / Neurons / Cell differentiation / Retinoblastoma protein / Cell cycle / E2F1 / Prader-Willi syndrome / Genomic imprinting / がん抑制遺伝子 / プラダー・ウイリ症候群 / necdin / 胚性がん細胞 / 核蛋白質 / アデノウィルスベクター / 神経分化 |
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| Research Abstract |
Neurons in the vertebrate central nervous system CNS withdraw permanently from the cell cycle immediately after differentiation from their proliferative progenitors. To study the molecular mechanism whereby neurons become postmitotic, we focused on the functional roles and molecular properties of necdin, a neuronal growth suppressor isolated from embryonal carcinoma P19 cells. Results obtained are as follows. [1] Necdin, like retinoblastoma protein (Rb), bound to transforming domains of simian virus 40 (SV40) large T antigen and adenovirus E1A.[2] Necdin bound to E2F-1, a cellular transcription factor that promotes the cell cycle, and suppressed its functions. [3] Ectopic expression of necdin in Rb-dificient SAOS-2 cells suppressed the cell growth, indicating that necdin is a functional substitute for Rb. [4] An antibody against recombinant necdin protein reacted with necdin in the cytoplasm of mouse brain neurons, and the immunoreactivity was the highest in the hypothalamus.[5] The 5'-end sequence of the human necdin gene contains frequent CpG dinucleotides (identified as a CpG island), and methylation in vitro of CpG dinucleotides in the promoter region suppressed the transcriptional activity. [6] The human necdin gene was localized to chromosome 15q11.2-q12, which lies within the region involved in Prader-Willi syndrome, a genomic imprinting-associated neurobehavioral disorder. [7] In summary, necdin suppresses cell growth in a manner similar to that of Rb, and its deficiency may cause the defect of neuronal differentiation.
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