REG gamma/PA28 gamma proteasome activator interacts with PML and Chk2 and affects PML nuclear bodies number

REG gamma (also called PA28 gamma or PSME3) is a proteasome activator involved in the degradation of several proteins that regulate cell cycle and transcription. Recently, we demonstrated that this protein has a role also in the maintenance of chromosomal stability and in the response to spindle damaging agents. Here we report for the first time that REG gamma interacts with the promyelocytic leukemia protein (PML), accumulates in PML nuclear bodies (PML-NBs), but it does not play any role in normal or arsenic-induced PML degradation. However, REG gamma seems to regulate PML-NBs number, since its deficiency causes an increase in PML-NBs, which can be overcome by increased levels of SUMO1, and its overexpression has the opposite effect. We additionally found that REG gamma interacts with the DNA damage checkpoint kinase Chk2, whose presence is necessary for the increase of PML-NBs induced by REG gamma deficiency, and that REG gamma depletion resulted in a partial restoration of PML-NBs in APL derived cells. Altogether, these results underline a new role for REG gamma in the control and regulation of PML subnuclear structures.