The proteasome activator PA28 binds to both ends of the central catalytic machine, known as the 20 S proteasome, in opposite orientations to form the enzymatically active proteasome. The PA28 family is composed of three members designated α, γ, and γ, PA28α and PA28β form the heteropolymer mainly located in the cytoplasm, whereas PA28γ forms a homopolymer that predominantly occurs in the nucleus. Available evidence indicates that the heteropolymer of PA28α and PA28β is involved in the processing of intracellular antigens, but the function of PA28γ remains elusive. To investigate the role of PA28γ in vivo, we generated mice deficient in the PA28γ gene. The PA28γ-deficient mice were born without appreciable abnormalities in all tissues examined, but their growth after birth was retarded compared with that of PA28γ(+/-) or PA28γ(+/+) mice. We also investigated the effects of the PA28γ deficiency using cultured embryonic fibroblasts
cells lacking PA28γ were larger and displayed a lower saturation density than their wild-type counterparts. Neither the expression of PA28α/β nor the subcellular localization of PA28α was affected in PA28γ(-/-) cells. These results indicate that PA28γ functions as a regulator of cell proliferation and body growth in mice and suggest that neither PA28α nor PA28β compensates for the PA28γ deficiency.