Disease relevance of PSMB10

• Infection with lymphocytic choriomeningitis virus (LCMV) elicited a markedly reduced cytotoxic T cell (CTL) response to the LCMV epitopes GP276-286/Db and NP205-212/Kb in MECL-1-/- mice [1].
• Invasion by Salmonella typhimurium induces increased expression of the LMP, MECL, and PA28 proteasome genes and changes in the peptide repertoire of HLA-B27 [2].
• However, LMP-10 showed a significant selective downmodulation in the metastases as well [3].

High impact information on PSMB10

• A subset of the proteasome beta-subunits (LMP2, LMP7, and MECL-1) and one of the accessory complexes, PA28, are upregulated by gamma-interferon and affect the generation of peptides to promote more efficient antigen recognition [4].
• When processed from their precursors, three pairs of the 10 homologous, but distinct, beta-type subunits of eukaryotic proteasomes, that is, X/LMP7, Y/LMP2, and Z/MECL1, have an NH2-terminal threonine residue, assumed to be part of a catalytic center [5].
• Molecular cloning of a cDNA encoding one subunit designated as Z, downregulated by IFN-gamma, showed that it is a novel proteasomal subunit with high homology to MECL1, which is markedly induced by IFN-gamma [5].
• LMP2 is required for MECL-1 incorporation at the level of proteasome precursor formation that guarantees the concerted incorporation of two IFN-gamma-inducible proteasome subunits encoded inside and outside the MHC [6].
• Combined deficiencies of these gene products were common, and marked deficiency of LMP10 was found in five of the nine cell lines with deficits [7].

Biological context of PSMB10

• Here we show that in mice, Lmp10 is a single-copy gene localized to chromosome 8, in a region of conserved synteny with human chromosome 16 [8].
• DNA sequence, chromosomal localization, and tissue expression of the mouse proteasome subunit lmp10 (Psmb10) gene [8].
• An A/G nucleotide polymorphism in PSMB10 intron 2 and a C/T single nucleotide polymorphism in exon 5 were detected by polymerase chain reaction restriction fragment length polymorphism [9].
• Utilizing biotinylated-epoxomicin as a molecular probe, we demonstrate that epoxomicin covalently binds to the LMP7, X, MECL1, and Z catalytic subunits of the proteasome [10].
• Low expression of the IFN-gamma-regulated beta low molecular mass polypeptide (Lmp)2, Lmp7, and MECL-1 was demonstrated in a panel of seven BL lines that express the germinal center cell phenotype of the original tumor [11].

Anatomical context of PSMB10

• The B cell line Daudi and the monocyte cell line THP-1 expressed MECL1 constitutively at an intermediate level [12].
• In cells unrelated to the immune system, a very low constitutive expression of MECL1 was detected, highly inducible by IFN-gamma [12].
• The porcine PSMB10 was mapped by somatic cell hybrid panel and radiation hybrid mapping on SSC6p14-p15, which is in good agreement with human-pig comparative maps [9].
• An altered T cell repertoire in MECL-1-deficient mice [1].
• The importance of these elements for IFN-gamma induction of MECL1 was addressed by transfecting an endothelial cell line with MECL1 promoter constructs [13].

Associations of PSMB10 with chemical compounds

• Utilizing LMP10 as an intracytoplasmic marker and calreticulin and tapasin as ER luminal markers, we show that the modified flow cytometry and cell-ELISA are sensitive, simple and reproducible methods to detect HLA class I antigen processing machinery components in cells [14].

Regulatory relationships of PSMB10

• To reveal the extent of constitutive and IFN-gamma-induced expression of MECL1, we studied MECL1 in different cell lines by Northern and Western blotting [12].
• Conversely, the uptake of LMP2 is strongly enhanced by MECL-1 expression [6].
• Co-transfection of IRF-1 resulted in induced MECL1 promoter activity in the absence of IFN-gamma [13].

Other interactions of PSMB10

• Identification of MECL-1 (LMP-10) as the third IFN-gamma-inducible proteasome subunit [15].
• During an immune response to pathogens, the proinflammatory cytokine interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha are released, which induce the proteasome subunits LMP2, LMP7, and MECL-1 [16].
• No association with vitiligo was found for the MECL1 gene, which encodes a third immunoproteasome subunit and is unlinked to the MHC class II region [17].
• The human MECL1 promoter contains two interferon-stimulated response elements (ISREs), generally known to bind members of the interferon regulatory factor (IRF) family [13].

Analytical, diagnostic and therapeutic context of PSMB10

• Immunoprecipitation of proteasomes and analysis on two-dimensional gels revealed that during maturation the inducible proteasome subunits LMP2, LMP7, and MECL-1 are up-regulated and that the neosynthesis of proteasomes is switched exclusively to the production of immunoproteasomes containing these subunits [18].
• The relative expression of six proteosome subunits (existing subunits X, Y, and Z and immunoproteosome subunits LMP7, LMP2, and MECL1) in 54 RCCs was investigated using RT-PCR analysis and was compared with clinicopathological measures, including patient outcome [19].

References