Ubiquitin-specific protease 28: the decipherment of its dual roles in cancer development

As significant posttranslational modifications, ubiquitination and deubiquitination, whose balance is modulated by ubiquitin-conjugating enzymes and deubiquitinating enzymes (DUBs), can regulate many biological processes, such as controlling cell cycle progression, signal transduction and transcriptional regulation. Belonging to DUBs, ubiquitin-specific protease 28 (USP28) plays an essential role in turning over ubiquitination and then contributing to the stabilization of quantities of substrates, including several cancer-related proteins. In previous studies, USP28 has been demonstrated to participate in the progression of various cancers. Nevertheless, several reports have recently shown that in addition to promoting cancers, USP28 can also play an oncostatic role in some cancers. In this review, we summarize the correlation between USP28 and tumor behaviors. We initially give a brief introduction of the structure and related biological functions of USP28, and we then introduce some concrete substrates of USP28 and the underlying molecular mechanisms. In addition, the regulation of the actions and expression of USP28 is also discussed. Moreover, we concentrate on the impacts of USP28 on diverse hallmarks of cancer and discuss whether USP28 can accelerate or inhibit tumor progression. Furthermore, clinical relevance, including impacting clinical prognosis, influencing therapy resistance and being the therapy target in some cancers, is depicted systematically. Thus, assistance may be given to future experimental designs by the information provided here, and the potential of targeting USP28 for cancer therapy is emphasized.