Regulation of the NRF2 Transcription Factor Activity Via SIRT1-Induced Deacetylation: Possible SIRT1–NRF2 Feedback Loop

NRF2 is a key component that is associated with protecting cells from damage. It is intersected by other signaling pathways that can have both direct and indirect effects on it. Proteins that can influence activity through acetylation and deacetylation, such as p300/CBP, HDACs and SIRT1, play an important role in these signaling pathways. But sometimes the research of different scientific groups contradict each other. On the one hand, there is evidence showing that acetylation increases the activity of NRF2, while deacetylation reduces the activity and level of transcripts of genes regulated by NRF2. On the other hand, some results show that activation of SIRT1 deacetylase increases the posttranslational activity of NRF2. At the same time, NRF2 itself affects the expression of SIRT1, forming a positive feedback loop. This review examines various aspects of the interaction between the activity of transcription factor NRF2 and acetylases/deacetylases, primarily SIRT1. In addition, variants of indirect interaction between NRF2 and SIRT1 through other signaling pathways associated with proteins such as PGC-1α and p62 are being considered.