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糖介导的非正规的无处不在会损害Nrf1/NFE2L1的激活
Yukiko Yoshida1, Tsuyoshi Takahashi2, Nozomi Ishii2
1Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Science, 2-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan.
Molecular cell
|August 8, 2024
概括
涉及SCFFBS2和ARIH1 E3连接酶的非传统的ubiquitination通路通过在N-glycan残留物上形成非典型的ubiquitin链来抑制核因子红色素-2-like 1 (Nrf1) 激活,从而阻碍蛋白质体基因转录.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 无处不在的路径 无处不在的路径
背景情况:
- 蛋白质酶抑制激活核因子红色素2-样1 (Nrf1) 蛋白质酶体基因转录.
- Nrf1的激活取决于DDI2的裂变和NGLY1的脱糖化.
- 之前的研究表明,SCFFBS2的Nrf1泛化会损害激活,但机制尚不清楚.
研究的目的:
- 阐明SCFFBS2介导的全方位化抑制Nrf1激活的分子机制.
- 为了识别Nrf1调节中涉及的E3连接酶和特定的泛位.
- 了解无处不在如何影响Nrf1与DDI2的相互作用.
主要方法:
- 同免疫沉试验研究E3酶相互作用.
- 在实验室内使用糖和重组蛋白进行无处不在的测试.
- 质谱测量用于识别无处不在的位和链类型.
- 在特定的E3连接酶和ubiquitin链的存在下对Nrf1激活的分析.
主要成果:
- SCFFBS2和ARIH1通过N-甘氨酸残留物上的氧键合作,使Nrf1无处不在.
- 来自N-甘氨酸的N-乙糖胺 (N-GlcNAc) 残留物作为无处不在的受体位.
- 在Nrf1.1.上,UBE2L3对于组装非典型的乌比奎丁链至关重要.
- 这些非典型的乌比奎丁链阻止了DDI2介导的Nrf1激活.
结论:
- 涉及SCFFBS2-ARIH1和UBE2L3的非传统的无处不在途径抑制了Nrf1的激活.
- 这条途径利用N-甘氨酸结构作为无处不在的对接点.
- 这些发现揭示了一个控制蛋白质体基因转录的新型调节机制.
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