Regulatory mechanism of expression of ETS transcription factor Myeloid elf-1-like factor (MEF) by tumor suppressors

抑癌基因对ETS转录因子髓样elf-1样因子(MEF)表达的调控机制

• 批准号: 23590082
• 负责人: SUICO Mary Ann Soten
• 金额: $ 3.41万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23590082/
• 关键词: 転写因子; がん抑制遺伝子; MEF; 低酸素; HIF1; ETS転写因子; 癌抑制遺伝子; 翻訳後発現調節; p53; MDM2; Rb; 翻訳後発現制御

Myeloid elf-1-like factor (MEF) functions as transcriptional factor and plays critical roles in development, cellular differentiation, proliferation, transformation and immune responses. In the present study, we aim to determine the regulatory mechanisms of MEF expression by several cellular factors. First, we demonstrated that tumor suppressor p53 decreases the level of MEF protein through the induction of transcription of MDM2, an E3 ubiquitin ligase. Moreover, the findings also revealed that another tumor suppressor Rb increases the MEF protein level possibly by stabilizing its protein expression. Finally, our data further showed that hypoxia increases both the mRNA and protein levels of MEF through HIF1alpha, the main effector molecule of hypoxia. On the whole, the findings revealed in these studies provide a better understanding of how the transcriptional regulator MEF is influenced by tumor suppressors such as p53 and Rb, and by hypoxia-related protein HIF1alpha.

髓样elf-1样因子（MEF）作为转录因子发挥作用，在发育、细胞分化、增殖、转化和免疫反应中发挥关键作用。在本研究中，我们的目的是确定几种细胞因子对 MEF 表达的调节机制。首先，我们证明肿瘤抑制因子 p53 通过诱导 MDM2（一种 E3 泛素连接酶）的转录来降低 MEF 蛋白的水平。此外，研究结果还表明，另一种肿瘤抑制因子Rb可能通过稳定其蛋白表达来增加MEF蛋白水平。最后，我们的数据进一步表明，缺氧通过缺氧的主要效应分子HIF1α增加MEF的mRNA和蛋白质水平。总的来说，这些研究揭示的结果让我们更好地了解转录调节因子 MEF 如何受到 p53 和 Rb 等肿瘤抑制因子以及缺氧相关蛋白 HIF1α 的影响。

项目成果

Hyperthermia with mild electrical stimulation protects pancreatic β-cells from cell stresses and apoptosis.

• DOI: 10.2337/db11-1098
• 发表时间: 2012-04
• 期刊: Diabetes
• 影响因子: 7.7
• 作者: Kondo T;Sasaki K;Matsuyama R;Morino-Koga S;Adachi H;Suico MA;Kawashima J;Motoshima H;Furukawa N;Kai H;Araki E
• 通讯作者: Araki E

MEF/ELF4 transactivation by E2F1 is inhibited by p53.

• DOI: 10.1093/nar/gkq762
• 发表时间: 2011-01
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: Taura M;Suico MA;Fukuda R;Koga T;Shuto T;Sato T;Morino-Koga S;Okada S;Kai H
• 通讯作者: Kai H

遺伝性腎疾患Alport症候群における癌抑制遺伝子p53の腎病態進行抑制機構の解明

阐明抑癌基因 p53 抑制遗传性肾病 Alport 综合征中肾病进展的机制

• 发表时间: 2011
• 作者: 福田 亮介 ;小山 皓介;古賀 友紹;甲斐 友佳理;メリーアン スイコ;首藤 剛;甲斐 広文
• 通讯作者: 甲斐 広文

Mild electrical stimulation and heat shock ameliorates progressive proteinuria and renal inflammation in mouse model of Alport syndrome.

轻度电刺激和热休克可改善阿尔波特综合征小鼠模型中进行性蛋白尿和肾脏炎症。

• DOI: 10.1371/journal.pone.0043852
• 发表时间: 2012
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Koga T;Kai Y;Fukuda R;Morino-Koga S;Suico MA;Koyama K;Sato T;Shuto T;Kai H
• 通讯作者: Kai H

Protective effects of p53 in a mouse model of progressive hereditary kidney disease Alport syndrome

p53 对进行性遗传性肾病 Alport 综合征小鼠模型的保护作用

• 发表时间: 2011
• 作者: Hiraide S;Ueno K;Yamaguchi T;Matsumoto M;Yanagawa Y;Yoshioka M;Togashi H;R. Fukuda
• 通讯作者: R. Fukuda