| First Author | Murata S | Year | 2001 |
| Journal | EMBO J | Volume | 20 |
| Issue | 21 | Pages | 5898-907 |
| PubMed ID | 11689430 | Mgi Jnum | J:72533 |
| Mgi Id | MGI:2153219 | Doi | 10.1093/emboj/20.21.5898 |
| Citation | Murata S, et al. (2001) Immunoproteasome assembly and antigen presentation in mice lacking both PA28alpha and PA28beta. EMBO J 20(21):5898-907 |
| abstractText | Two members of the proteasome activator, PA28alpha and PA28beta, form a heteropolymer that binds to both ends of the 20S proteasome. Evidence in vitro indicates that this interferon-gamma (IFN-gamma)-inducible heteropolymer is involved in the processing of intracellular antigens, but its functions in vivo remain elusive. To investigate the role of PA28alpha/beta in vivo, we generated mice deficient in both PA28alpha and PA28beta genes. The ATP-dependent proteolytic activities were decreased in PA28alpha(-/-)/beta(-/-) cells, suggesting that 'hybrid proteasomes' are involved in protein degradation. Treatment of PA28alpha(-/-)/beta(-/-) cells with IFN-gamma resulted in sufficient induction of the 'immunoproteasome'. Moreover, splenocytes from PA28alpha(-/-)/beta(-/-) mice displayed no apparent defects in processing of ovalbumin. These results are in marked contrast to the previous finding that immunoproteasome assembly and immune responses were impaired in PA28beta(-/-) mice. PA28alpha(-/-)/beta(-/-) mice also showed apparently normal immune responses against infection with influenza A virus. However, they almost completely lost the ability to process a melanoma antigen TRP2-derived peptide. Hence, PA28alpha/beta is not a prerequisite for antigen presentation in general, but plays an essential role for the processing of certain antigens. |
