Identification of Novel Acetylation Sites in Nrf1 (NFE2L1) and Their Regulation by Sirtuin 1 (SIRT1)

For cells to survive the damages of reactive oxygen species they must defend themselves. Cellular defense is accomplished by means of the antioxidant response element (ARE). One of the main factors involved in regulating the ARE is the nuclear factor (erythroid-derived 2)-like1 protein (Nrf1), this protein has not been thoroughly characterized, so the manner in which it is regulated is unknown. The deacetylase Sirtuin 1 (SIRT1) has been shown to regulate a relative of Nrf1, Nrf2. When SIRT1 was chemically inhibited, the acetylation of Nrf1 increased, indicating SIRT1 to be a regulator of Nrf1. When Nrf1 was deacetylated by SIRT1, a significant decrease in the activity of Nrf1 was observed. Under hypoxic conditions, it was observed that SIRT1 was a stronger regulator of Nrf1 activity than hypoxia. Two acetylation sites were identified in Nrf1; lysines 205 and 629. The deacetylation of Nrf1 resulted in a significant decrease in cellular senescence(definition).