Proteasome activator 28γ (PA28γ) binds to and activates the proteasome in an ATP-independent manner to promote mainly ubiquitin-independent protein degradation in cells. Previously, four transcript variants of PA28γ have been identified, which have been closely correlated with the progression of cancers. In the present study, we predicted the alternative splicing of PA28γ via the bioinformatics tool ASPicDB and 49 splices were predicted. Then, we cloned some new segment according to predication in oral cancer cells using reverse transcription PCR and a novel variant of PA28γ was found. The novel transcript encodes a truncated form compared with other isoforms of PA28γ. However, it contains most of the conserved residues and the 'activation loop' of the PA28γ family. In order to explore its function, we overexpressed the variant in HEK293 cells and demonstrated that this variant is likely to further regulate cell cycle and apoptosis via regulating p53 and the mouse double minute2 homolog (Mdm2).