| Project/Area Number |
15591166
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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 |
Dermatology
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| Research Institution | Tohoku University |
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Principal Investigator |
OKUYAMA Ryuhei Tohoku University, Hospital, Lecturer, 病院, 講師 (80292332)
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| Co-Investigator(Kenkyū-buntansha) |
IKAWA Shuntaro Tohoku University, Institute of Development, Aging, and Cancer, Associate Professor, 加齢医学研究所, 助教授 (50241576)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2003: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | Notch / p51 / p53 / Keratinocytes / Epithelial cells / Differentiation / 細胞増殖 / 転写因子 / シグナル伝達 / 発癌 / 乾癬 |
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| Research Abstract |
Although basal keratinocytes express Notch1 that induces growth arrest and cell differentiation in keratinocytes, they maintain undifferentiated state, suggestive of an unidentified factor(s) couteracting with Notch function specifically in basal keratinocytes. p51, p53 homolog, is expressed chiefly in basal keratinocytes, and is suggested as not only a marker for keratinocyte stem cells but also a prerequisite for the formation of epidermis. We demonstrate that p51 maintains undifferentiated cell characters through suppression of Notch activity. HES-1 promoter activity, showing Notch activity, was suppressed by ΔNp51B, the predominant p51 isoform expressed in keratinocytes. Interestingly, similar suppression of HES-1 promoter activity was also-occurred by TAp51B, which is expected to have opposite molecular functions because TA isoforms have transactivation domain while ΔN isoforms do not. We introduced p51 adenovirus expression vectors together with Notch1 into primary mouse keratinocytes, and then examined undifferentiated cell characters. ΔNp51B cancelled Notch1 induced growth arrest and downregulation of integrin expression. Co-expression of p51 restored undifferentiated cell characters against Notch1 expression. Our data reveal that p51 maintains undifferentiation condition of keratinocytes through the inhibition of Notch signal, and this balance tightly connects with determining keratinocyte cell commitment.
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