AUTHOR=Zhang Xiuzhen , Meng Tong , Cui Shuaishuai , Feng Ling , Liu Dongwu , Pang Qiuxiang , Wang Ping TITLE=Ubiquitination of Nonhistone Proteins in Cancer Development and Treatment JOURNAL=Frontiers in Oncology VOLUME=10 YEAR=2021 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.621294 DOI=10.3389/fonc.2020.621294 ISSN=2234-943X ABSTRACT=

Ubiquitination, a crucial post-translation modification, regulates the localization and stability of the substrate proteins including nonhistone proteins. The ubiquitin-proteasome system (UPS) on nonhistone proteins plays a critical role in many cellular processes such as DNA repair, transcription, signal transduction, and apoptosis. Its dysregulation induces various diseases including cancer, and the identification of this process may provide potential therapeutic targets for cancer treatment. In this review, we summarize the regulatory roles of key UPS members on major nonhistone substrates in cancer-related processes, such as cell cycle, cell proliferation, apoptosis, DNA damage repair, inflammation, and T cell dysfunction in cancer. In addition, we also highlight novel therapeutic interventions targeting the UPS members (E1s, E2s, E3s, proteasomes, and deubiquitinating enzymes). Furthermore, we discuss the application of proteolysis-targeting chimeras (PROTACs) technology as a novel anticancer therapeutic strategy in modulating protein target levels with the aid of UPS.