3.6.2. Discovery of anti-apoptotic properties of PA28γ

Initial studies on PA28γ-deficient mice suggested a role for PA28γ as a regulator of cell proliferation and body growth [90]. Lack of PA28γ did not affect expression of other PSME family members such as PA28α or PA28β and resulted in smaller body size. Entry into S phase was impeded and number of G1 cells increased. MEFs depleted in PA28γ revealed increased spontaneous apoptosis during logarithmic growth.

Recently, we demonstrated a correlation between cellular PA28γ levels and the sensitivity of cells toward apoptosis in different cellular contexts, thereby confirming a role of proteasome activator PA28γ as an anti-apoptotic regulator [46]. We investigated the anti-apoptotic role of PA28γ upon UV-C stimulation in B8 mouse fibroblasts stably overexpressing the PA28γencoding PSME3 gene and upon butyrate-induced apoptosis in human HT29 adenocarcinoma cells with silenced PSME3 genes. Interestingly, our results demonstrate that PA28γ has a strong influence on different apoptotic hallmarks, especially the levels of transcriptionally active phosphorylated p53, BclXL, and active effector caspases (Figure 2) [46].
