Degradation Factor 1 was discovered 20 years ago as a yeast protein copurifying with Rad26, a helicase involved in transcription-coupled DNA repair. It was subsequently shown to control the ubiquitylation and destruction of the large subunit of DNA damage-arrested RNA Polymerase II. Since that time, much has been learned about Def1′s role in polymerase destruction and new functions of the protein have been revealed. We now understand that Def1 is involved in more than just RNA polymerase II regulation. Most of its known functions are associated with maintaining chromosome and genomic integrity, but other exciting activities outside this realm have been suggested. Here we review this fascinating protein, describe its regulation and present a hypothesis that Def1 is a central coordinator of ubiquitin signaling pathways in cells.

降解因子 1 在 20 年前被发现是一种与 Rad26 共同纯化的酵母蛋白，Rad26 是一种参与转录偶联 DNA 修复的解旋酶。随后显示它可以控制 DNA 损伤抑制 RNA 聚合酶 II 的大亚基的泛素化和破坏。从那时起，人们对 Def1 在聚合酶破坏中的作用有了很多了解，并且揭示了该蛋白质的新功能。我们现在了解到 Def1 不仅仅参与 RNA 聚合酶 II 的调节。它的大多数已知功能与维持染色体和基因组完整性有关，但已经提出了该领域之外的其他令人兴奋的活动。在这里，我们回顾了这种迷人的蛋白质，描述了它的调节并提出了一个假设，即 Def1 是细胞中泛素信号通路的中心协调者。