Cellular models of memory formation have focused on the need for protein synthesis. Recently, evidence has emerged that protein degradation mediated by the ubiquitin-proteasome system (UPS) is also important for this process. This has led to revised cellular models of memory formation that focus on a balance between protein degradation and synthesis. However, protein degradation is only one function of the UPS. Studies using single-celled organisms have shown that non-proteolytic ubiquitin-proteasome signaling is involved in histone modifications and DNA methylation, suggesting that ubiquitin and the proteasome can regulate chromatin remodeling independent of protein degradation. Despite this evidence, the idea that the UPS is more than a protein degradation pathway has not been examined in the context of memory formation. In this article, we summarize recent findings implicating protein degradation in memory formation and discuss various ways in which both ubiquitin signaling and the proteasome could act independently to regulate epigenetic-mediated transcriptional processes necessary for learning-dependent synaptic plasticity. We conclude by proposing comprehensive models of how non-proteolytic functions of the UPS could work in concert to control epigenetic regulation of the cellular memory consolidation process, which will serve as a framework for future studies examining the role of the UPS in memory formation.

记忆形成的细胞模型集中在蛋白质合成的需求上。最近，有证据表明，由泛素-蛋白酶体系统（UPS）介导的蛋白质降解对于该过程也很重要。这导致了修订的记忆形成细胞模型，该模型专注于蛋白质降解与合成之间的平衡。但是，蛋白质降解只是UPS的功能之一。使用单细胞生物的研究表明，非蛋白水解的泛素-蛋白酶体信号传导参与组蛋白修饰和DNA甲基化，这表明泛素和蛋白酶体可以独立于蛋白质降解来调节染色质重塑。尽管有这些证据，但在记忆形成的背景下，UPS不仅仅是蛋白质降解途径的想法尚未得到检验。在本文中，我们总结了在记忆形成中涉及蛋白质降解的最新发现，并讨论了泛素信号传导和蛋白酶体可以独立发挥作用来调节学习依赖的突触可塑性所必需的表观遗传介导的转录过程的各种方式。我们通过提出关于UPS的非蛋白水解功能如何协同工作以控制细胞记忆整合过程的表观遗传学调控的综合模型的结论，这将作为今后研究UPS在记忆形成中作用的框架。