REGgamma/PA28gamma proteasome activator interacts with PML and Chk2 and affects PML nuclear bodies number.
REGgamma (also called PA28gamma 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 REGgamma 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, REGgamma 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 REGgamma interacts with the DNA damage checkpoint kinase Chk2, whose presence is necessary for the increase of PML-NBs induced by REGgamma deficiency, and that REGgamma depletion resulted in a partial restoration of PML-NBs in APL derived cells. Altogether, these results underline a new role for REGgamma in the control and regulation of PML subnuclear structures.
Zannini
Laura
L
Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milano 20133, Italy. laura.zannini@istitutotumori.mi.it
Buscemi
Giacomo
G
Fontanella
Enrico
E
Lisanti
Sofia
S
Delia
Domenico
D
D001324:Autoantigens / Q000378:metabolism*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000201:enzymology* / Q000648:ultrastructure; D064447:Checkpoint Kinase 2; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D045586:Intranuclear Inclusion Bodies / Q000378:metabolism* / Q000648:ultrastructure; D009687:Nuclear Proteins / Q000378:metabolism*; D000071156:Promyelocytic Leukemia Protein; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D025842:SUMO-1 Protein / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D001324:Autoantigens; C099558:Ki antigen; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D025842:SUMO-1 Protein; C495501:SUMO1 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases; D046988:Proteasome Endopeptidase Complex