Disease relevance of Serpina3g

• Serpina3g down-regulation was controlled by a hypoxia inducible factor (HIF) mechanism [1].
• Spi2A upregulation protected lymphocytic choriomeningitis virus-specific memory progenitors from programmed cell death [2].
• Serpin 2a (spi2a) expression is also induced in macrophages in vivo during infection with Salmonella typhimurium and Listeria monocytogenes, and in vitro by a variety of bacteria and bacterial products [3].
• Examination of the reactivities of the MAbs by immunofluorescence staining of tissue sections showed that one of the antibodies, MAb 2A2, reacted with luminal epithelium of the mammary gland and spontaneous mammary carcinomas of SHN mice [4].

High impact information on Serpina3g

• Serine protease inhibitor 2A is a protective factor for memory T cell development [2].
• Thus, Spi2A promotes the survival of cytotoxic T lymphocytes, allowing them to differentiate into memory CD8 T cells [2].
• Here we report that the gene encoding serine protease inhibitor 2A (Spi2A), an inhibitor of lysosomal executioner proteases dependent on transcription factor NF-kappaB, is upregulated in memory cell precursors [2].
• The murine Spi-2 proteinase inhibitor locus: a multigene family with a hypervariable reactive site domain [5].
• Sequence analysis of this gene has identified it as a serine protease inhibitor EB22/3 (serpin 2A) [6].

Biological context of Serpina3g

• Serpina3g gene expression returned to basal levels following Ni removal, suggesting that the observed silencing was a dynamic and reversible process [1].
• Expression of serpin 2A also showed a marked up regulation during the activation of cytotoxic suppressor CD8+ T cells, with a clear lag between the appearance of transcript and detection of protein [6].
• Serine protease inhibitor 2A inhibits caspase-independent cell death [7].
• After immunoaffinity purification of the MAb 2A2-recognized antigen and determination of its N-terminal amino acid sequence, we identified the antigen as Ly-6D, also known as ThB, which belongs to a family of glycosyl-phosphatidylinositol-anchored cell surface proteins [4].
• The gene for the alpha chain of the IL2 receptor in the mouse, Il-2ra, localizes to bands 2A2 or 2A3 on Chromosome 2 [8].

Anatomical context of Serpina3g

• Constitutive expression of serpin 2A in FDCP-Mix cells was associated with an increase in the clonogenic potential of the cells and with a delay in the appearance of fully mature cells in cultures undergoing granulocyte macrophage differentiation when compared with control cells [6].
• Interestingly, Spi2 over-expression is not occurring in olfactory neurons but in cells of the lamina propria, suggesting that Spi2 may act extracellularly as a cell death inducer [9].
• In contrast, mutant 2A2 exhibits reduced but detectable levels of H2-DMa message and DMalpha protein only after treatment with IL-4, which induces the expression of both the H2-DMa and the H2-DMb genes in B cells [10].
• The distribution of these antigens (designated as 2A2 and 2G10) was almost identical in human germ cell tumors in which they hallmarked yolk sac components and some tubular endodermal structures [11].
• Further examination of the tissue lysates by western blot analysis revealed that MAb 2A2 reacts with a 17-kDa antigen expressed in normal mammary epithelial cells and mammary carcinoma cells [4].

Associations of Serpina3g with chemical compounds

• The epitope of 2A2 is unknown but is different from that of CML and fluorolink or other known AGE structures such as pyrraline, pentosidine, and crosslines [12].
• A alpha k-reactive mAbs 1E9, 2A2, and 3F12 recognize an epitope that includes the polymorphic residue 44 of the A alpha k polypeptide, and the A alpha k-reactive antibody, K24-199, recognizes a conformationally determined epitope influenced by residues from all three polymorphic regions [13].
• This first report showing abnormal expression of EAAT4, GABRA6, Spi2 combined with lower levels of glutamate and GABA are likely to be associated with the pathophysiology of CD [14].

Regulatory relationships of Serpina3g

• In the absence of caspase activity, Spi2A suppressed PCD by inhibiting cathepsin B after it was released into the cytoplasm [7].
• The cytokine IFN-gamma also induces spi2a expression in macrophages, and this induction is synergistic with bacterial products [3].

Other interactions of Serpina3g

• We conclude that inhibition of lysosomal executioner proteases by Spi2A is a physiological mechanism by which cells are protected from caspase-independent programmed cell death [7].
• Although many protein targets have been described for ubiquitin conjugation, spi2a is the first ISG15-modified protein to be reported [3].

Analytical, diagnostic and therapeutic context of Serpina3g

• Serpina3g, a member of the mouse serpin family, was among the most down-regulated genes (32-fold) in response to Ni exposure of mouse cells based on the Affymetrix gene chip [1].
• The MAILA assay has been used in our laboratory to the determination of the type of HLA molecule recognized by human monoclonal antibodies 91C2 (anti-A2 + 28), 34F11 (anti-DQ1), and 2A2 (anti-DQ1 + 4 + short DQ7), using well characterized monomorphic as well as polymorphic murine monoclonals for the specific immobilization of HLA molecules [15].
• The decrease of GABRA6 and high expression of Spi2 in CD mouse brain were also confirmed by real-time RT-PCR [14].

References