Deubiquitination Reactions on the Proteasome for Proteasome Versatility

International Journal of Molecular Sciences

Byung-Hoon Lee¹  Hyeonjeong Park¹  JiYeong Shin¹  Srinivasan Muniyappan¹  Non-Nuoc Tran¹  SungBae Lee² 

[1] Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Korea;Protein Dynamics-based Proteotoxicity Control Lab, Basic Research Lab, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Korea;

关键词: proteasome;    proteolysis;    ubiquitin;    deubiquitination;    deubiquitinating enzyme;    USP14;   

DOI  :  10.3390/ijms21155312

来源: DOAJ

【 摘 要 】

The 26S proteasome, a master player in proteolysis, is the most complex and meticulously contextured protease in eukaryotic cells. While capable of hosting thousands of discrete substrates due to the selective recognition of ubiquitin tags, this protease complex is also dynamically checked through diverse regulatory mechanisms. The proteasome’s versatility ensures precise control over active proteolysis, yet prevents runaway or futile degradation of many essential cellular proteins. Among the multi-layered processes regulating the proteasome’s proteolysis, deubiquitination reactions are prominent because they not only recycle ubiquitins, but also impose a critical checkpoint for substrate degradation on the proteasome. Of note, three distinct classes of deubiquitinating enzymes—USP14, RPN11, and UCH37—are associated with the 19S subunits of the human proteasome. Recent biochemical and structural studies suggest that these enzymes exert dynamic influence over proteasome output with limited redundancy, and at times act in opposition. Such distinct activities occur spatially on the proteasome, temporally through substrate processing, and differentially for ubiquitin topology. Therefore, deubiquitinating enzymes on the proteasome may fine-tune the degradation depending on various cellular contexts and for dynamic proteolysis outcomes. Given that the proteasome is among the most important drug targets, the biology of proteasome-associated deubiquitination should be further elucidated for its potential targeting in human diseases.

【 授权许可】

Unknown