泛素化在細胞自噬分解酵母菌胞內蛋白質中 所扮演的角色

Role of ubiquitylation in autophagic degradation of cytosolic soluble protein in Saccharomyces cerevisiae

劉昂宇(Ang-Yu Liu)

指導教授 ： 黃偉邦

國立臺灣大學/生命科學院/動物學研究所/碩士(2010年)

https://doi.org/10.6342/NTU.2010.02190

摘要

泛素是種小而保守的蛋白質，普遍的被用來標定在真核生物中將要被蛋白脢體分解的異常構型蛋白質。細胞自噬則是真核生物中另一條降解蛋白質的路徑；透過由雙層膜包裹的細胞質所形成的自噬小體與細胞中的液胞或溶小體進行融合，細胞能有效的分解胞器以及蛋白質，以獲得養分應付充滿壓力的環境。已知在哺乳動物細胞中，被泛素所標定的蛋白質除了透過蛋白脢體分解外，也會形成蛋白質聚集體，堆積在細胞質當中，而這些蛋白質聚集體，已被證實能選擇性的透過細胞自噬所清除。這次研究，我們發現在酵母菌中泛素修飾並不會促進蛋白質形成聚集體，且泛素化的修飾不但不會促進蛋白質透過細胞自噬分解，反而扮演著抑制性的角色。我們同時發現，泛素的一個已知的突變能破壞泛素與大部分泛素結合區的交互作用，而這種泛素突變也喪失抑制細胞自噬分解蛋白質的作用。我們認為，透過泛素與某種未知蛋白質的交互作用，阻礙了泛素化蛋白質被自噬小體包裹的過程。這個發現，是泛素抑制細胞自噬分解作用的首件案例。

關鍵字

泛素

並列摘要

Ubiquitin is a small, conserved molecule among eukaryotes that serves as a tag for the breakdown of misfolded-proteins by the 26s proteasome in eukaryotes. Autophagy is another protein turnover process, which sequesters cytoplasm into double membrane vesicles, called autophagosomes. Subsequent fusion with the vacuole/lysosome mediates breakdown of proteins or organelles in eukaryotes facing stressful environments. In mammalian cells, ubiquitylated protein aggregates in cytosol associated with neural degeneration diseases were shown to be specific substrates for autophagic degradation. However, in this study, we showed that the ubiquitin modification does not trigger the formation of protein aggregates in saccharomyces cerevisiae. Moreover, we found that ubiquitylation impedes, instead promotes, the degradation of cytosolic proteins by starvation-induced autophagy in yeast. We also identified an ubiquitin mutant, which was previously shown defective in interacting with most known ubiquitin-binding domains (UBD), lost the delay on autophagic degradation of cytosolic proteins. We propose that the interaction of ubiquitin with an unknown factor prevents sequestration of ubiquitylated cytosolic soluble proteins into autophagosomes for degradation. This is the first report indicating that ubiquitylation of cargo proteins hinder their autophagic degradation.

並列關鍵字

Ubiquitin ； Ubiquitylation ； Autophagy

參考文獻

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