p53 homologue, p51/p63, controls keratinocyte proliferation/differentiation due to Notch activity

p53 同源物 p51/p63 通过 Notch 活性控制角质形成细胞增殖/分化

• 批准号: 17591154
• 负责人: OKUYAMA Ryuhei
• 金额: $ 2.24万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591154/
• 关键词: Dermatology; Keratinocytes; p51; Notch; 皮膚

p53 homologue, p51/ p63, predominantly expressed in keratinocyte stem cells, is indispensable for the formation of epidermis. Notch1, another such gene indispensable for the process, induces growth arrest and differentiation in keratinocytes. We found that exogenous expression of ΔNp51B (ΔNp63α), one of the isoforms of p51 specifically expressed in basal keratinocytes, blocked Notch 1 dependent growth arrest and differentiation in mouse keratinocytes by inhibiting p21 expression and maintaining integrins expression. Furthermore, ΔNp51B by itself was found to have ability to induce expression of integrin α6β4, which promotes attachment of basal cells to basal membrane thereby keeping the cells in immature state. Therefore, we conclude that ΔNp51B expression warrants integrin expression even under the influence of Notch1 and that ΔNp51B is a long-sought factor required to maintain basal cell keratinocytes immaturity by inhibiting Notch activity. We will postulate a plausible model explaining the maintenance of the squamous epithelium architectures as well as offering mechanistic explanations for pathological features of skin diseases, including cancers, psoriasis along with physiological wound healings.

p53同源物p51/p63主要在角质形成细胞中表达，对于表皮形成是必不可少的。 Notch1是该过程必不可少的另一种基因，它诱导角质形成细胞的生长停滞和分化。我们发现ΔNP51B（ΔNP63α）的外源表达是在基本角质形成细胞中特异性表达的p51的同工型之一，阻断了Notch 1依赖性生长停滞和小鼠角质形成细胞的分化，通过抑制p21表达和保持整合素表达。此外，发现ΔNP51b本身具有影响整联蛋白α6β4的表达的能力，该能力促进了基本细胞与碱性膜上的附着，从而使细胞保持不成熟的状态。因此，我们包括即使在Notch1的影响下，ΔNP51B表达警告整联蛋白的表达也是ΔNP51B是通过抑制Notch活性来维持基本细胞角质形成细胞不成熟所需的长期因素。我们将假设一个合理的模型，该模型解释了方形上皮体系结构的维持，并为皮肤病的病理特征提供机械解释，包括癌症，牛皮癣以及身体伤口愈合。

项目成果

p53 Homologue, p51/p63, Maintains the Immaturity of Keratinocyte Stem Cells by Inhibitinq Notch1 Activity.

p53 同源物 p51/p63 通过抑制 Notch1 活性维持角质形成细胞干细胞的不成熟。

• 发表时间: 2007
• 期刊: Oncogene (In Press)
• 作者: Okuyama R;et al.
• 通讯作者: et al.

p51/p63, a novel p53 homologue, potentates p53 activity and is a human cancer gene therapy candidate.

p51/p63 是一种新型 p53 同源物，可增强 p53 活性，是人类癌症基因治疗的候选者。

• 发表时间: 2006
• 期刊: j Gene Med 8
• 作者: Kunisaki R;Ikawa S;Maeda T;Nakazaki Y;Kurita R.Harata M;Shutoh Y;Bai YS;Soda Y;Tanabe T;Dobi T;Kato R;Ikawa Y;Asano S;Tani K.
• 通讯作者: Tani K.

Stimulation of Dmc1-mediated DNAA strand exchange by the human Rad54B protein.

人 Rad54B 蛋白刺激 Dmc1 介导的 DNAA 链交换。

• 发表时间: 2006
• 期刊: Nucleic Acid Res 34
• 作者: Shirai S;et al.
• 通讯作者: et al.