Figure 5. Regulation of SIRT1 nucleocytoplasmic shuttling by oxidative stress.
Oxidative stress causes oxidative and carbonyl modifications as well as nucleocytoplasmic shuttling of SIRT1 to the cytoplasm. This will decrease SIRT1 protein levels through proteasomal degradation in the cytoplasm. At the same time, the transcription of NF-κB-dependent pro-inflammatory genes is increased once SIRT1 is reduced. Intracellular redox status (i.e., GSH/GSSG ratio) can also affect nucleocytoplasmic shuttling of SIRT1. NES, Nuclear export sequences.