ABSTRACT
During the normal process of biological growth and development, NF-E2-related factor 1 (Nrf1/ Nfe2l1) plays a unique role in maintaining intracellular homeostasis and organ integrity. The deficiency of Nrf1 will lead to severe oxidative stress, genomic instability, and result in liver cancer, neurodegenerative disorder and other diseases. In recent years, it has been found that Nrf1 could yield different activated isoforms or even opposite activity isoforms in a variety of ways to perform distinct functions, and the distribution of these isoforms may play a vital role in the process of tumor development. Therefore, to gain a better understanding of the function of Nrf1 isoforms in cells and tissues, we first briefly introduced its discovery process, and demonstrated the multiple mechanisms of distinct isoform production including selective shear processing, internal selective translation initiation, and post-translation shear processing. More importantly, three different post-translational processing models, transmembrane dynamic processing, site-specific processing, ubiquitin-dependent processing, were expounded in detail. Furthermore, the biological function of different isoforms of Nrf1 and its role in diseases were also summarized in the last section. Collectively, we focus on the production mechanism of different isoforms of Nrf1 and their roles in diseases so as to lay a foundation for finding new strategies for tumor treatment.