控制TGFβ信号通过E3无素合酶TRIP12的无素独立功能控制TGFβ信号
Kripa S Keyan1, Safa Salim1, Swetha Gowda1
1College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar.
Cell death & disease
|October 20, 2023
概括
在E3泛基因酶TRIP12调节转化生长因子β (TGFβ) 信号,独立于其酶活性. TRIP12通过调节SMAD4无化来控制细胞命运,影响癌症等疾病.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 转化生长因子β (TGFβ) 途径对于调节细胞功能至关重要,其失调与癌症和自身免疫性疾病等疾病有关.
- 了解控制TGFβ信号的分子机制对于开发治疗策略至关重要.
研究的目的:
- 为了研究HECT域E3泛基因酶TRIP12在调节TGFβ信号传递中的作用.
- 阐明TRIP12控制TGFβ通路活性的分子机制.
主要方法:
- 在人类,小鼠和Drosophila模型中利用了基因操纵 (CRISPR/Cas9,基因淘汰).
- 研究了SMAD4.的蛋白质-蛋白质相互作用和无处不在状态.
- 评估了TGFβ通路激活,细胞增殖,分化和迁移.
主要成果:
- TRIP12通过招募SMURF2到SMAD4来控制TGFβ信号,独立于其E3酶活性,从而促进其抑制性单双化.
- 在各种模型中,TRIP12的遗传抑制强烈激活TGFβ信号,影响细胞增殖,分化和迁移.
- 在TGFβ信号传递中TRIP12的作用是从Drosophila到哺乳动物的进化保存.
结论:
- TRIP12作为TGFβ信号传递的关键,进化保守的调节器.
- TRIP12对TGFβ通路活性的调节对理解和潜在治疗涉及TGFβ失调的疾病,包括癌症,有影响.
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