Figure 8: DJ-1 regulates 20S proteasome activity.
From: The Parkinson’s-associated protein DJ-1 regulates the 20S proteasome
Our results indicate that DJ-1 physically binds the 20S proteasome and inhibits its function, independent of the oxidative modifications of Cys106 to sulfinic acid. Previous studies and our results indicate that under oxidative stress, DJ-1 stabilizes Nrf2, the antioxidant stress response transcription factor, which leads to the expression of NQO1 (refs 49, 70). NQO1 reinforces the function of DJ-1 by binding to the 20S proteasome and preventing proteolysis36,37. Nrf2, on the other hand, also promotes the expression of 20S proteasome subunits25,65, in accordance with the cell’s need to rapidly eliminate oxidatively damaged proteins. This robust regulatory mechanism is probably necessary to sustain the balance between the need to efficiently eliminate oxidatively damaged proteins, ensure proper proteasomal function and maintain the abundance of the naturally unfolded proteins. Green arrows indicate activation and red lines ending in a bar represent inhibition.
