自噬系统和蛋白酶体系统之间的相互联系

在真核细胞中已发现两条主要降解途径,即自噬系统和蛋白酶体系统．长期以来,这两条降解途径一直被认作是完全独立的路径,然而最近的证据强烈提示,这两条主要降解途径之间相互联系．其中,发现干扰这两条途径的任一条可影响另一条途径的活性,抑制蛋白酶体可刺激自噬活性．同时发现泛素的作用比先前想象更广泛,不仅具有标记蛋白酶体降解蛋白质这一 “经典作用”,还涉及自噬-溶酶体途径降解底物泛素化,是这些主要降解途径的共同标签．这些降解系统分享某些底物和调节分子,显示协同作用,在某些背景下,显示补偿功能．降解系统之间的协同和补偿作用在许多细胞过程中显得至关重要．因此这些降解系统异常或联系失常不仅导致细胞功能的异常,而且也与多种重要疾病的发生和发展密切相关．对这些降解途径功能及其联系的深入了解可拓展人们对这些降解途径的认识,有助于对多种细胞分解代谢过程的深入理解,也有助于相关新药的研发．

Crosstalk Between Autophagy and Proteasome Systems

The two major degradation pathways of eukaryotic cells, autophagy- lysosome and ubiquitin- proteasome systems, have been found. The two degradation pathways were, for a long time, regarded as independent degradation pathways. However, recent evidence strongly suggest that there is crosstalk between the two degradation pathways. For example, perturbations either pathway have been reported to affect the activity of the other pathway. And inhibition of proteasome may stimulate autophagy activity. The roles of ubiquitin are also found far more than previously imagined. Ubiquitin not only has "traditional function" targeting proteins for proteasome degradation, but also is involved in ubiquitylating substrates for degradation of autophagy- lysosome system. So ubiquitin is a common tag of these main degradation pathways. These degradation systems share certain substrates and regulators, and show coordinated and, in some contexts, compensatory function. The coordinated and compensatory relationship between these degradation systems that becomes critical in many cellular processes. Therefore, abnormities in these degradation systems involves not only aberrant cellular functions but also occurrence and development of many diseases. Understanding functions and crosstalk of these major degradation pathways will provide further insights into the repertoire of these degradation pathways, help to understand diverse cellular catabolic processes and facilitate our development of related new drugs.