REGγ/PA28γ proteasome activator interacts with PML and Chk2 and affects PML nuclear bodies number

REGγ (also called PA28γ 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 REGγ interacts with the promy-elocytic 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, REGγ 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 REGγ interacts with the DNA damage checkpoint kinase Chk2, whose presence is necessary for the increase of PML-NBs induced by REGγ deficiency, and that REGγ depletion resulted in a partial restoration of PML-NBs in APL derived cells. Altogether, these results underline a new role for REGγ in the control and regulation of PML subnuclear structures.