确定XAF1作为一种内源性AKT抑制剂
Min Chen1, Kangjunjie Wang2, Ying Han3
1State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, CAS Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China.
Cell reports
|June 29, 2023
概括
与XIAP相关的因子 (XAF1) 通过阻止其无处不在的活性,直接抑制AKT1激酶激活. 缺少XAF1促进AKT的激活,影响新陈代谢和前列腺癌的发展.
科学领域:
- 分子生物学分子生物学
- 细胞信号传递 细胞信号传递
- 癌症生物学 癌症生物学
背景情况:
- AKT激酶对细胞代谢和生存至关重要,激活受到严格调节.
- 失调的AKT信号与代谢障碍和癌症有关.
研究的目的:
- 为了确定AKT1激酶活性的新型调节剂.
- 研究XAF1在AKT信号传递中的作用及其对代谢疾病和前列腺癌的影响.
主要方法:
- 共同免疫沉用于识别相互作用的蛋白质.
- 西方斑点测试用于评估蛋白质的泛化和酸化.
- 在小鼠模型中进行基因淘汰和子宫外表达研究.
- 对人类前列腺癌样本的分析.
主要成果:
- XAF1直接与AKT1结合,抑制其与K63结合的多基化和激活.
- Xaf1淘汰导致小鼠组织中的AKT激活,减少饮食引起的肥胖和胰岛素抵抗.
- 减少XAF1表达与前列腺癌中增加的p-AKT相关,而Xaf1缺乏会加速小鼠的瘤生长.
- 通过FOXO1转录调节,XAF1与AKT1形成负反循环.
结论:
- XAF1 作为 AKT1 信号传输的新型负调节剂.
- 调节XAF1水平对代谢疾病和前列腺癌具有治疗潜力.
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