非泛素依赖地降解蛋白质研究进展

The Research Advances in Ubiquitin-independent Degradation of Proteins

如何识别和选择性降解蛋白质是细胞生命过程中非常重要的环节,泛素-蛋白酶体需能降解途径的发现,揭示了蛋白质在细胞内选择性降解的普遍方式,成为研究焦点.然而,很少关注蛋白酶体以非泛素依赖方式降解蛋白质的可能性.近年来,已发现不少蛋白质被蛋白酶体以非泛素依赖方式降解.该途径涉及降解某些短寿命的调节蛋白、错误折叠蛋白、衰老蛋白和氧化蛋白,以及新合成蛋白的"质量控制",并涉及病理过程如癌症、神经退行性疾病,所以具有非常重要的生理和病理作用.总结了近一二十年来发现的一些具有代表性的被蛋白酶体以非泛素依赖方式降解的蛋白质,并重点论述了其作用的分子机制,以期以点带面地展示这一领域的研究概况.

How the proteins are recognized and selectively degraded in the cellular life process is an important scientific question. The general mode of selective degradation of proteins in the cell in ATP- and ubiquitin-dependent pathway has been well studied. However, little attention has been directed toward the possible involvement of the proteasome in ubiquitin-independent proteolysis. In the past few years, many publications have provided evidence that the proteasome can degrade some proteins in a ubiquitin-independent manner. This pathway is involved in the elimination of some short-life regulated proteins, misfolded proteins, aged proteins and oxidized proteins as well as ＂quality control＂ of newly synthesized proteins, and involved in pathological processes such as cancer and neurodegenerative diseases. Therefore, it plays important roles in physiology and pathology. Some representative proteins degraded by the proteasome in a ubiquitin-independent manner in the past decade or two were summarized with focuses on their molecular mechanisms and the selected cases as examples to provide an overview of the field.