PA28 subunits of the mouse proteasome: primary structures and chromosomal localization of the genes

Abstract

The 20S proteasome is a multi-subunit protease responsible for the production of peptides presented by major histocompatibility complex (MHC) class I molecules. Recent evidence indicates that an interferon-gamma (IFN-gamma)-inducible PA28 activator complex enhances the generation of class I binding peptides by altering the cleavage pattern of the proteasome. In the present study, we determined the primary structures of the mouse PA28 alpha- and beta-subunits. The deduced amino acid sequences of the alpha- and beta-subunits were 49% identical. We also determined the primary structure of the mouse PA28 gamma-subunit (Ki antigen), a protein of unknown function structurally related to the alpha- and beta-subunits. The amino acid sequence identity of the gamma-subunit to the alpha- and beta-subunits was 40% and 32%, respectively. Interspecific backcross mapping showed that the mouse genes coding for the alpha- and beta-subunits (designated Psme1 and Psme2, respectively) are tightly linked and map close to the Atp5g1 locus on chromosome 14. Thus, unlike the LMP2 and LMP7 subunits, the IFN-gamma-inducible subunits of PA28 are encoded outside the MHC. The gene coding for the gamma-subunit (designated Psme3) was mapped to the vicinity of the Brca1 locus on chromosome 11. A computer search of the DNA databases identified a gamma-subunit-like protein in ticks and Caenorhabditis elegans, the organisms with no adaptive immune system. It appears that the IFN-gamma-inducible alpha- and beta-subunits emerged by gene duplication from a gamma-subunit-like precursor.

Growth Retardation in Mice Lacking the Proteasome Activator PA28γ

“…These results indicate that PA28␥ is unlikely to play a pivotal role in the MHC class I antigen processing/presentation system. This is consistent with the observation that PA28␥ has been found in invertebrates that do not have the adaptive immune system (26). However, the present study does not rule out the possibility that PA28␥ plays a specialized role in antigen presentation such as the processing of antigens in the nucleus.…”

“…Construction of the PA28␥ Targeting Vector-A 12-kb NotI fragment containing the entire coding region of the PA28␥ gene was obtained from a 129/SvJ mouse genomic library (Stratagene) as previously reported (26,27). The targeting vector consisted of the 6.2-kb genomic DNA containing the 1.2-kb neomycin resistance gene derived from pMC1neopoly(A) (see Fig.…”

A Novel Role for PA28γ-Proteasome in Nuclear Speckle Organization and SR Protein Trafficking

“…It is thought to play an important role in the production of MHC class I antigenic peptides (Groettrup et al, 1996). PA28␥, initially called "Ki antigen," is similar to PA28␣ and ␤ (Kandil et al, 1997;Tanahashi et al, 1997), but forms only homoheptamers and is mostly nuclear. Its functions are poorly characterized, but studies in mice (Murata et al, 1999;Barton et al, 2004) and flies (Masson et al, 2003) suggest a role for this complex in cell cycle progression and apoptosis.…”

Full-length coding sequences and mapping of porcine <i>ATP6VOE</i> and <i>ATP5G1</i> genes

“…In mouse (Kandil et al, 1997) this gene is tightly linked to Psme1 and Psme2 which have been shown to be highly expressed in lung, spleen and liver tissue in pig (Wang et al, 2004) suggesting that ATP5G1 might be related to animal immunity.…”