Disease relevance of PSME2

• Full-length cDNAs for three human proteasome activator subunits, called REGalpha, REGbeta, and REGgamma, have been expressed in Escherichia coli, and the purified recombinant proteins have been characterized [1].

High impact information on PSME2

• Corresponding amino acid substitutions in REGbeta (N135Y) and REGgamma (N151Y) produce inactive proteins that also bind the proteasome and inhibit proteasome activation by their normal counterparts [2].
• In contrast to such extreme deficiencies, we found unaltered or only partially decreased expression of PA28alpha and PA28beta in tumor cell lines [3].
• Recombinant alpha and beta subunits bind each other with high affinity, and the REGalpha/beta heteromeric complex activates hydrolysis of LLVY-methylcoumaryl-7-amide (LLVY-MCA) and LLE-beta-nitroanilide (LLE-betaNA) more than REGalpha or REGbeta alone [1].
• REGalpha and REGbeta activate the trypsin-like, chymotrypsin-like and peptidylglutamyl-preferring active sites, whereas REGgamma only activates the proteasome's trypsin-like subunit [4].
• Activated T and B cells had up-regulated PA28 beta expression at the mRNA level [5].

Biological context of PSME2

• The 5' end of the mouse, but not the human, gene coding for PA28 beta undergoes alternative splicing that is predicted to alter the N-terminal amino acid sequence [6].
• REGgamma differs from REGalpha and REGbeta in that it markedly stimulates hydrolysis of peptides with basic residues in the P1 position but only modestly activates cleavage of LLVY-MCA or LLE-betaNA by the proteasome [1].
• Molecular cloning of proteasome activator PA28-beta subunit of large yellow croaker (Pseudosciana crocea) and its coordinated up-regulation with MHC class I alpha-chain and beta(2)-microglobulin in poly I:C-treated fish [7].

Anatomical context of PSME2

• REG, purified from red blood cells, is a complex of REG alpha and REG beta subunits [8].
• At the protein level, RAPA inhibited PA28 alpha and PA28 beta in the activated T cells according to immunoblotting and confocal microscopy [5].

Associations of PSME2 with chemical compounds

• It exists as a unique homopolymer under non-denaturing conditions. gamma-IFN was found to induce the expression of PA28 alpha and PA28 beta, whereas it caused almost complete loss of the PA28 gamma protein in cells [9].
• The intron/exon organization of both genes was highly conserved, the major difference being the absence of the exon encoding the lysine and glutamic acid-rich 'KEKE' motif in PA28beta [10].

Physical interactions of PSME2

• Each subunit is capable of activating the proteasome, and when combined, they form superactive REGalpha/REGbeta complexes [11].

Co-localisations of PSME2

• PA28alpha and PA28beta are co-localized in the cell whereas PA28gamma has a different distribution [12].

Other interactions of PSME2

• Genomic clones were obtained for the genes encoding the beta subunits of the human proteasome and for the associated proteasome activators PA28alpha and beta (PSME1 and PSME2, respectively) [13].

Analytical, diagnostic and therapeutic context of PSME2

• METHODS: Real time quantitative RT-PCR was used to analyse the mRNA expression pattern of the proteasome activator subunits PA28alpha and PA28beta and of constitutive proteasome and interferon-gamma-inducible immunoproteasome subunits in peripheral blood mononuclear cells [14].

References