Nucleotide sequence analysis of the ~35-kb segment containing interferon-γ-inducible mouse proteasome activator genes

Abstract.

The proteasome activator PA28 is an interferon-γ-inducible complex made up of two related subunits, named PA28α and PA28β, with approximately 50% amino acid sequence identity. Accumulated evidence indicates that binding of this complex to the 20S proteasome enhances the generation of class I-binding peptides. Previously, we showed that the genes coding for PA28α and PA28β, designated Psme1 and Psme2, respectively, are located ~6 kb apart with their 3′ ends pointing toward each other on mouse Chromosome 14. In the present study, we sequenced the regions adjacent to Psme1 and Psme2. In a contiguous stretch of ~35 kb, we identified six genes arranged in the following order: Cg10671-like (a gene similar to Drosophila CG10671)–Psme1–Cgi112 (a ubiquitously expressed gene with no known function)–Psme2–Flj10111 (a gene coding for a protein with two RING finger domains)–Isgf3g (an interferon-γ-inducible gene coding for an interferon-dependent, positive-acting transcription factor 3γ). Interestingly, the 3′ untranslated region of Psme1 overlaps with that of Cgi112 by 7 bp. Database analysis indicates that the corresponding human genes also overlap by up to 7 bp in their 3′ untranslated regions. The 5′ end of the mouse, but not the human, gene coding for PA28β undergoes alternative splicing that is predicted to alter the N-terminal amino acid sequence. Comparison of the mouse sequence with a human draft sequence deposited in the NCBI database revealed that the overall organization of the region coding for the interferon-γ-inducible proteasome activator is conserved between human and mouse.