Proteasomes and proteasome activator 200 kDa (PA200) accumulate on chromatin in response to ionizing radiation.
Proteasome activator 200 kDa (PA200) forms nuclear foci after exposure of cells to ionizing radiation and enhances proteasome activity in vitro. Within cells, it is unclear whether PA200 responds to radiation alone or in association with proteasomes. In the present study, we identified three forms of cellular PA200 (termed PA200i, ii and iii) at the mRNA and protein levels. Neither PA200ii nor PA200iii appears to associate with proteasomes. All detectable PA200i is associated with proteasomes, which indicates that PA200i and proteasomes function together within the cell. Consistent with this idea, we find that exposure of cells to radiation leads to an equivalent accumulation of both PA200i and core proteasomes on chromatin. This increase in PA200 and proteasomes on chromatin is not specific to the stage of cell cycle arrest since it occurs in cells that arrest in G(2)/M and cells that arrest in G(1)/S after exposure to radiation. These data provide evidence that PA200 and proteasomes function together within cells and respond to a specific radiation-induced damage independent of the stage of cell cycle arrest.
Blickwedehl
Jennifer
J
Department of Immunology, Rosewell Park Cancer Institute, Buffalo, NY 14263, USA.
McEvoy
Sarah
S
Wong
Irene
I
Kousis
Philaretos
P
Clements
James
J
Elliott
Rosemary
R
Cresswell
Peter
P
Liang
Ping
P
Bangia
Naveen
N
D002453:Cell Cycle / Q000528:radiation effects*; D002843:Chromatin / Q000502:physiology* / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism* / Q000528:radiation effects*; D011829:Radiation Dosage; D011839:Radiation, Ionizing; D015398:Signal Transduction / Q000528:radiation effects
D002843:Chromatin; D009687:Nuclear Proteins; D046988:Proteasome Endopeptidase Complex; C521188:PSME4 protein, human