Disease relevance of Psme1

• A mouse fibroblast line expressing the murine cytomegalovirus pp89 protein was transfected with either the human or murine gene encoding the PA28alpha subunit, which is sufficient to activate the peptide-hydrolysing activity of the 20S proteasome in vitro [1].
• Overexpression of the proteasome subunits LMP2, LMP7, and MECL-1, but not PA28 alpha/beta, enhances the presentation of an immunodominant lymphocytic choriomeningitis virus T cell epitope [2].

High impact information on Psme1

• Here we report that enhanced expression of PA28alpha at a level similar to that obtained after IFN-gamma induction resulted in a marked enhancement of recognition by pp89-specific cytotoxic T cells; the presentation of influenza nucleoprotein was also significantly improved [1].
• A role for the proteasome regulator PA28alpha in antigen presentation [1].
• It is shown here that mice with a disrupted PA28b gene lack PA28a and PA28b polypeptides, demonstrating that PA28 functions as a hetero-oligomer in vivo [3].
• Secondly, we show the presence of a functional NF-kappaB site in the PA28beta promoter, which is absent in the PA28alpha promoter, indicating regulation of PA28beta expression by transcription factors of the NF-kappaB family [4].
• The proteasome regulator PA28alpha/beta was up-regulated, whereas PA28gamma was reduced in the liver of lymphocytic choriomeningitis virus-infected mice [5].

Biological context of Psme1

• Using reverse transcription polymerase chain reaction, we cloned and sequenced full-length mouse cDNAs for the two homologous subunits of the proteasome activator PA28 (PA28alpha and PA28beta), as well as for the related protein Ki [6].
• Northern blot analysis of PA28a, PA28b, and Ki mRNA demonstrated broad tissue distribution [6].
• Although single transcripts were detected for PA28a and PA28b, two different sized transcripts were detected for mouse Ki, suggesting either alternative splicing or alternate polyadenylation sites [6].
• Immunoproteasome assembly and antigen presentation in mice lacking both PA28alpha and PA28beta [7].
• These results indicate that PA28gamma functions as a regulator of cell proliferation and body growth in mice and suggest that neither PA28alpha nor PA28beta compensates for the PA28gamma deficiency [8].

Anatomical context of Psme1

• However, by northernblot and immunoprecipitation experiments we show that while PA28alpha is able to act alone the observed effect in the PA28beta and PA28alphabeta transfectant cell lines is due to increased levels of PA28alphabeta complexes [9].

Associations of Psme1 with chemical compounds

• The PA28 family is composed of three members designated alpha, beta, and gamma; PA28alpha and PA28beta form the heteropolymer mainly located in the cytoplasm, whereas PA28gamma forms a homopolymer that predominantly occurs in the nucleus [8].
• METHODS: C57BL/6 or the proteasome activator PA28alpha-knockout mice were intradermally inoculated with 1% formalin-fixed B16 cells three times at weekly intervals either before or after tumor challenge [10].
• (4) The amount of proteasome activator 28 alpha subunit (PA28), magnesium dependent protein phosphatase (MDPP) and lysophospholipase 2 was decreased 6 h after LPS treatment but recovered or up-regulated 24 and 30 h after LPS treatment [11].

Regulatory relationships of Psme1

• The proteasome regulator PA28alpha/beta can enhance antigen presentation without affecting 20S proteasome subunit composition [12].

Other interactions of Psme1

• Two members of the proteasome activator, PA28alpha and PA28beta, form a heteropolymer that binds to both ends of the 20S proteasome [7].
• The proteasome catalytic beta subunits LMP2, LMP7, and MECL-1 and two proteasome activator proteins, PA28 alpha and beta, are induced following exposure to IFN-gamma in vitro [13].
• PA28alpha/beta appeared not to be required for the development of CD8+ T cells, although it is known to be essential for the development of CD8+ T cells specific for tyrosinase-related protein-2, one of melanocyte-lineage differentiated antigens [10].
• The histocompatibility class I molecule H2-Q10 (HA10_MOUSE) and proteasome activator PA28 alpha-subunit (PSME1_MOUSE) were found up-regulated in ANXB1 DNA immunized mice, which may contribute to the augmented activation of T lymphocytes [14].

References