Neuroprotective Function of 14-3-3 Proteins in Neurodegeneration

Figure 2

Overview of the molecular basis of 14-3-3 antiapoptotic activity. 14-3-3 proteins inhibit apoptosis through multiple mechanisms including regulating the subcellular localization of pro- and antiapoptotic proteins. 14-3-3 binds to Bad and Bax to sequester them in the cytoplasm. Similarly, SRPK2 and FOXO1 are retained in the cytoplasm through 14-3-3 binding. Cdc25 is exported from the nucleus through a 14-3-3 interaction. SRPK2, FOXO1, and Cdc25 contribute to cell cycle reentry and subsequent apoptosis. Further, the death-promoting activity of ASK1 is antagonized by its binding to 14-3-3 proteins.