Characterization of the mouse proteasome regulator PA28b gene.

Abstract

The proteasome regulator PA28, which can be upregulated by IFN, is important in the modulation of proteasome activity. Since the proteasome has been implicated in the processing of the major histocompatibility complex (MHC) class I antigens, it was of interest to determine the regulatory elements of PA28 at the genomic level. Although PA28 has been found in different species, the gene layout on the chromosome was not determined. In this study, the genetic organization of mouse PA28b was characterized. Two copies of the PA28b gene, namely b1 and b2, were found by restriction fragment mapping and Southern hybridization. By fluorescence in situ hybridization, the location of the two PA28b genes was determined on chromosomes 11 and 14. PA28b1 has 11 exons, whereas PA28b2 has no introns and appears to be a nonfunctional pseudogene. The 5' promoter region of PA28b1 contains several transcriptional factor binding sites including two IFN responsive elements. The expression levels of PA28 and other gene products involved in MHC class I antigen presentation appear to be correlated in various tissues. Notably, PA28 is expressed at high levels in immunological tissues such as spleen and peripheral blood leukocytes. Taken together, PA28 seems to be co-regulated with other molecules involved in MHC class I antigen presentation.