SCF^<Fbxl12>modulates the abundance of p21 in concert with proteasome activator PA28γ

SCF^<Fbxl12>与蛋白酶体激活剂 PA28γ 一起调节 p21 的丰度

• 批准号: 23770218
• 负责人: TSURUTA Fuminori
• 金额: $ 2.91万
• 依托单位: University of Tsukuba
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23770218/
• 关键词: 細胞周期; タンパク質分解; ユビキチン; プロテアソーム; DNAダメージ; DNA損傷

The ubiquitin-proteasome system (UPS) plays an important role for the regulation of cell cycle and DNA damage response. The SCF complexes are the major ubiquitin ligases that control these processes. In this study, we found that SCF^<Fbxl12>associates with proteasomal subunit PA28γ and cyclin-dependent kinase (CDK) inhibitor p21, and is involved in the regulation of p21 abundance in cell. In addition, this complex-forming ability is attenuated by UV stimulation. We also found that the intronic regions of Fbxl12 acts as an alternative promoter and induces expression of short form of Fbxl12 in response to UV irradiation. Taken together, these data demonstrate that Fbxl12 is a key mediator that links UV irradiation to p21 degradation, and this novel function of Fbxl12 may provide an insight into the mechanisms by which DNA damage mediates p21 stabilization.

泛素-蛋白酶体系统（UPS）在细胞周期和DNA损伤反应的调节中发挥着重要作用。 SCF 复合物是控制这些过程的主要泛素连接酶。在本研究中，我们发现SCF^<Fbxl12>与蛋白酶体亚基PA28γ和细胞周期蛋白依赖性激酶（CDK）抑制剂p21相关，并参与细胞中p21丰度的调节。此外，这种复合物形成能力会因紫外线刺激而减弱。我们还发现 Fbxl12 的内含子区域充当替代启动子，并响应紫外线照射诱导短形式 Fbxl12 的表达。总而言之，这些数据表明 Fbxl12 是将紫外线照射与 p21 降解联系起来的关键介质，Fbxl12 的这种新功能可能有助于深入了解 DNA 损伤介导 p21 稳定的机制。

项目成果

Myeloma overexpressed 2 (Myeov2) regulates L11 subnuclear localization through Nedd8 modification.

• DOI: 10.1371/journal.pone.0065285
• 发表时间: 2013
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Ebina M;Tsuruta F;Katoh MC;Kigoshi Y;Someya A;Chiba T
• 通讯作者: Chiba T

SCF^<Fbl12> Is a Novel Mediator that Controls p21 Degradation

SCF^<Fbl12> 是一种控制 p21 降解的新型介体

• 发表时间: 2012
• 作者: 鶴田文憲;千葉智樹
• 通讯作者: 千葉智樹

A Ub ligase that target p21 is transcriptionally regulated by UV-irradiation.

靶向 p21 的 Ub 连接酶受紫外线照射进行转录调节。

• 发表时间: 2011
• 作者: Fuminori Tsuruta;Tomoki Chiba
• 通讯作者: Tomoki Chiba

SCF^<Fbl12>controls DNA damage-induced cell cycle arrest

SCF^<Fbl12>控制 DNA 损伤诱导的细胞周期停滞

• 发表时间: 2012
• 作者: 鶴田文憲;武部愛;海老名真度;阿部光;千葉智樹
• 通讯作者: 千葉智樹

SCFFbxl12 controls DNA damage-induced cell cycle

SCFFbxl12 控制 DNA 损伤诱导的细胞周期

• 发表时间: 2012
• 作者: Fuminori Tsuruta;Tomoki Chiba
• 通讯作者: Tomoki Chiba