Characterization of the Mouse PA28 Activator Complex Gene Family: Complete Organizations of the Three Member Genes and a Physical Map of the ∼150-kb Region Containing the α- and β-Subunit Genes

The proteasome is a multisubunit protease responsible for the generation of peptides loaded onto MHC class I molecules. Recent evidence indicates that binding of an IFN-γ-inducible PA28 activator complex to the 20S proteasome enhances the generation of class I binding peptides. The α- and β-subunits, which constitute the PA28 activator complex in the form of an (αβ)3 heterohexamer, show significant amino acid sequence similarity to a protein, designated Ki or the γ-subunit, that is capable of binding to the 20S proteasome. In this study, we describe the complete nucleotide sequences of the mouse genes, Psme1, Psme2, and Psme3, coding for the α-, β-, and γ-subunits, respectively. The overall exon-intron organizations of the three Psme genes are virtually identical, thus providing evidence that they are descended from a single ancestral gene. The promoter regions of the Psme1 and Psme2 genes contain sequence motifs that qualify as IFN-stimulated response elements, consistent with the observation that their expression is induced strongly by IFN-γ. The Psme1 and Psme2 genes are located ∼6 kb apart with their 3′-ends pointing toward each other on bands C2 to D1 of mouse chromosome 14, supporting the idea that they emerged by tandem duplication.