| Project/Area Number |
10480217
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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, Osaka University, 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, Osaka University, Instructor, たんぱく質研究所, 助手 (20260309)
TANIURA Hideo Institute for Protein Research, Osaka University, Instructor, たんぱく質研究所, 助手 (80263325)
NIINOBE Michio Institute for Protein Research, Osaka University, Associate Professor, たんぱく質研究所, 助教授 (80135748)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥9,700,000 (Direct Cost: ¥9,700,000)
Fiscal Year 1999: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1998: ¥7,100,000 (Direct Cost: ¥7,100,000)
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| Keywords | Neuron / Cell cycle / Necdin / E2F1 / p53 / Apoptosis / Proteasome / Genome imprinting / 細胞分裂終了 / アデノウイルスベクター / プラダー・ウイリ症候群 |
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| Research Abstract |
Neurons in the central nervous system withdraw from the cell cycle in an irreversible manner after their differentiation from neural stem cells and never proliferate throughout their lifetimes. The permanent mitotic arrest is the most fundamental phenotype displayed by differentiated neurons. The present study focused on the effects of necdin, a neural differentiation-specific protein, and its interactions with the cell cycle regulatory proteins E2F and p53. The research results are as follows. [1] Necdin bound to the transcription factor E2F1 and suppressed transcription of various genes involved in DNA replication. [2] Necdin bound to the transactivation domain of p53 and suppresses p53-dependent transcriptional activity. In addition, necdin suppressed p53-induced apoptosis. [3] Necdin functioned as a transcription factor that binds to specific DNA sequences. [4] The human necdin gene is localized in chromosome 15q11-q12, which is the region responsible for the pathogenesis of the Prader-Willi syndrome, a genome imprinting-associated neurogenic disorder. Necdin was expressed only from the paternal allele as determined using necdin gene knockout mice. [5] E2F1 mRNA was expressed in postmitotic neurons, and the E2F1 protein was degraded in the proteasome. [6] Postmitotic neurons underwent apoptosis when E2F1 was overexpressed. [7] The above findings suggest that necdin interacts with cell cycle regulatory factors E2F1 and p53 and plays an important role in terminally differentiation and maintenance of differentiation phenotypes.
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