本期文章：《科学》：Volume 381 Issue 6660

美国哈佛医学院Michael E. Greenberg等研究人员合作发现，midnolin-蛋白酶体通路捕捉蛋白质进行泛素化非依赖的降解。这一研究成果于2023年8月25日发表在国际学术期刊《科学》上。

研究人员发现midnolin促进了许多核蛋白的破坏，包括由即时早期基因编码的转录因子。多种刺激诱导了midnolin，而midnolin的过表达足以通过一种不需要泛素化的机制导致其靶标降解。相反，midnolin通过一个α螺旋与蛋白酶体结合，利用其Catch结构域与底物中可形成β链的区域结合，并利用泛素样结构域促进底物的破坏。因此，midnolin包含三个区域，它们协同作用，将大量核蛋白靶向蛋白酶体降解。

据了解，细胞利用泛素来标记蛋白酶体降解的蛋白质。尽管蛋白酶体也会消除未泛素化的蛋白质，但其机理尚不清楚。

附：英文原文

Title: The midnolin-proteasome pathway catches proteins for ubiquitination-independent degradation

Author: Xin Gu, Christopher Nardone, Nolan Kamitaki, Aoyue Mao, Stephen J. Elledge, Michael E. Greenberg

Issue&Volume: 2023-08-25

Abstract: Cells use ubiquitin to mark proteins for proteasomal degradation. Although the proteasome also eliminates proteins that are not ubiquitinated, how this occurs mechanistically is unclear. Here, we found that midnolin promoted the destruction of many nuclear proteins, including transcription factors encoded by the immediate-early genes. Diverse stimuli induced midnolin, and its overexpression was sufficient to cause the degradation of its targets by a mechanism that did not require ubiquitination. Instead, midnolin associated with the proteasome via an α helix, used its Catch domain to bind a region within substrates that can form a β strand, and used a ubiquitin-like domain to promote substrate destruction. Thus, midnolin contains three regions that function in concert to target a large set of nuclear proteins to the proteasome for degradation.

DOI: 10.1126/science.adh5021