Role of Forkhead Transcription Factors in Diabetes-Induced Oxidative Stress
Figure 1
(a) Model of FOXO regulation during ROS-induced oxidative stress. In response to ROS-induced oxidative stress, the activity of FOXO proteins is modulated by various posttranslational modifications including phosphorylation and acetylation. The stress-activated kinase JNK phosphorylates FOXO leading to its nuclear translocation and activation. FOXO is acetylated by acetyltransferase CBP/p300 upon oxidative stress stimuli and deacetylated by SIRT1 deacetylase. Change in the acetylation status may activate or inhibit FOXO activity depending on the target genes and experimental conditions. Activation of FOXO by various posttranslational modifications leads to the induction of stress response genes such as MnSOD, catalase, and GADD45α. (b) Negative regulation of FOXO by growth factor signaling. Upon growth factor stimulation, AKT phosphorylates FOXO proteins on conserved residues, leading to their nuclear exclusion. SKP2-dependent ubiquitination, which may be induced by Akt, leads to its subsequent degradation. P: phosphorylation; Ac: acetylation; Ub: ubiquitination.
