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通过UBR1-和arginylation驱动的内和自蛋白质质量控制重编程内溶酶蛋白质稳定性疾病压力

Ben B Wang¹, Pirjo M Apaja^1,2,3

¹South Australian Health and Medical Research Institute, Lifelong Health, Organelle Proteostasis Diseases, Adelaide 5000, South Australia, Australia.

Autophagy reports

|May 21, 2025

概括

蛋白质质量控制依赖于全方位联酶UBR1来管理细胞压力. 通过依赖 arginylation 的自细胞,UBR1 对于在内溶酶体压力期间维持蛋白质稳定至关重要,影响人类疾病.

科学领域:

细胞生物学细胞生物学
分子生物学分子生物学
生物化学生化学

背景情况:

蛋白质质量控制 (PQC) 维持细胞蛋白质稳定,但其在压力下内溶酶体通路中的机制尚不清楚.
内溶体应激,特别是涉及膜蛋白和累积应激,为PQC带来了独特的挑战.
在这些应激反应中,特定的基酶的作用是一个活跃的研究领域.

研究的目的:

调查乌比奎丁结合酶UBR1在内溶酶途径蛋白质质量控制中的作用.
阐明UBR1对内体和/或细胞质增加介导的蛋白质稳定应激反应的机制.
为了确定 arginylation,内和自在UBR1-介导的PQC中的参与.

主要方法:

鉴定了UBR1作为E3泛基因酶,参与蛋白质稳定应激.
分析UBR1在应对内体压力和增加时的ubiquitination和 arginylation.
对UBR1-SQSTM1/p62货物的选择性内体自 (内) 和自通路的研究.
评估UBR1或阿尔基尼化损失对内溶酶体通路功能的影响.

主要成果:

确定了UBR1作为一种关键的E3泛基因酶,用于因内体或细胞质Ca2+增加引起的蛋白质稳定应激.
压力条件激活了无处不在的和的UBR1-SQSTM1/p62货物的自和内通路.
丢失UBR1或化导致了内溶体通路的压力,表明它们的重要作用.

结论:

通过依赖 arginylation 的内和自,UBR1 在蛋白质稳定性扰乱期间对蛋白质质量控制至关重要.
这项研究强调了UBR1在压力诱导的自中发挥的关键作用及其对人类疾病的影响,这些疾病涉及内溶性酶体功能障碍.

关键词:

在SQSTM1/p62中使用.自吸菌体自吸菌体自吸菌体内部体内体内体内体内体内体内体内体内 lysosome 溶解酶体是如何形成的蛋白质稳定应激应变的压力复兴再生是一种再生方式.无处不在的化

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