Browsing by Author "Yamamoto, Y."

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Cytotoxic T-Lymphocyte Antigen-2 alpha participates in axial skeletogenesis during mouse embryo development
(Tanzania Veterinary Journal, 2015-05-25) Aligawesa, E.; Luziga, C. D.; Bui, T. N.; Kashoma, I. P.; Yamamoto, Y.
Cytotoxic T-lymphocyte antigen-2 alpha (CTLA-2α) has been discovered and expressed in mouse activated T-cells and mast cells. Structurally, it is homologous to the proregion of mouse cathepsin L, a lysosomal cystein proteinase. Expressed recombinant CTLA-2α is shown to exhibit selective inhibition to cathepsin L and is localized in the uterus during pregnancy where it is implicated in embryo plantation and development. CTLA-2α has also been demonstrated in the maternal side of the placenta in the deciduas basalis, metrial gland and myometrium layers in mouse but its vivo targets in the embryo are yet to be identified. We carried out studies to investigate the specific cell types synthesizing CTLA-2α protein in mouse embryo and examine its cellular localization. Immunofluorescence labeling showed intense localization of CTLA-2α in the cranium, vertebrae of cervical and thoracic region and the sternabrae. In the visceral organs, staining level was strong in the pancreas. Moderate staining was visible within the brain and remnants of the notochord. The rest of the organs including the spleen, small intestine and lungs were delineated by CTLA-2α. These findings suggest that CTLA-2α participates in an important role from the potential commitment of mesenchymal cells lineages to the ossification of axial skeleton early in embryogenesis.
Cytotoxic T-lymphocyte antigen-2 alpha participates in axial skeletogenesis during mouse embryo development
(Tanzania Veterinary Journal, 2015-02-12) Luziga, C. D.; Bui, T. N.; Kashoma, I. P.; Aligawesa, E.; Yamamoto, Y.
Cytotoxic T-lymphocyte antigen-2 alpha (CTLA-2α) has been discovered and expressed in mouse activated T-cells and mast cells. Structurally, it is homologous to the proregion of mouse cathepsin L, a lysosomal cystein proteinase. Expressed recombinant CTLA-2α is shown to exhibit selective inhibition to cathepsin L and is localized in the uterus during pregnancy where it is implicated in embryo plantation and development. CTLA-2α has also been demonstrated in the maternal side of the placenta in the deciduas basalis, metrial gland and myometrium layers in mouse but its vivo targets in the embryo are yet to be identified. We carried out studies to investigate the specific cell types synthesizing CTLA-2α protein in mouse embryo and examine its cellular localization. Immunofluorescence labeling showed intense localization of CTLA-2α in the cranium, vertebrae of cervical and thoracic region and the sternabrae. In the visceral organs, staining level was strong in the pancreas. Moderate staining was visible within the brain and remnants of the notochord. The rest of the organs including the spleen, small intestine and lungs were delineated by CTLA-2α. These findings suggest that CTLA-2α participates in an important role from the potential commitment of mesenchymal cells lineages to the ossification of axial skeleton early in embryogenesis.
Identification and characterization of the interactive proteins with cytotoxic T-lymphocyte antigen-2α
(2014-12-17) Luziga, C.; Yamamoto, Y.; Yamamoto, M.; Nga, B. T.; Kusakabe, K. T.
Cytotoxic T-lymphocyte antigen-2α (CTLA-2α) is a potent inhibitor of cathepsin L-like cysteine proteases. Recombinant CTLA-2α is known to be a potent, competitive inhibitor of cathepsin L-like cysteine proteases. In this study, cathepsin L, cathepsin C, and tubulointerstitial nephritis antigen-related protein 1 (TINAGL1) were identified as novel interactive proteins of CTLA-2α by the yeast two-hybrid screening system. The direct interactions and colocalization of these proteins with CTLA-2α were confirmed using co-immunoprecipitation and immunofluorescence staining, respectively. The disulfidebonded CTLA-2α/cathepsin L complex was isolated from mouse tissue. CTLA-2α was found to be specific and consistently expressed on the maternal side of the mouse placenta. Double immunofluorescence analysis showed that CTLA-2α was co-localized with cathepsin L, cathepsin C, and TINAGL1 in placenta. A simple cell-based fluorescence assay revealed that CTLA-2α exhibited inhibitory activity toward cathepsin C in live cells, which indicated that CTLA-2α is a novel endogenous inhibitor of cathepsin C.
Propeptide-like cysteine protease inhibitors: Structural properties, Mechanisms of inhibition and emerging roles in biological tissues
(Current Topics in Peptide & Protein Research., 2016-05-01) Luziga, C.; Nga, B.; Yamamoto, Y.
Propeptides of cysteine proteases including papain and cathepsins B, K, L, and S are selective inhibitors of their cognate cysteine proteases. A new class of endogenous inhibitors homologous to the propeptide regions of cysteine proteases has been identified and characterized in the past few decades. These include the mouse cytotoxic T-lymphocyte antigen-2 (CTLA-2), Bombyx cysteine proteinase inhibitor (BCPI), Drosophila crammer, and salmon salarin. They have been categorized as I29 (CTLA family) in the MEROPS peptidase database. In this review, we summarized experimental findings on their molecular forms, inhibition mechanisms, and biological functions. The overall properties of these inhibitors, molecular structures and inhibition mechanisms were found to be similar to those of propeptides of cysteine proteases. CTLA-2 has been shown to possess a unique inhibition mechanism by blocking its cognate enzyme, cathepsin L, through oxidizing the active thiol residue of the enzyme with its own thiol residue. The divergent biological functions of these inhibitors have been determined based on their inhibitory activities towards cathepsin L-like cysteine proteases. CTLA-2 is strongly expressed in the placenta, and may play roles in implantation and decidualization. It is also an inducer of Treg cells in the eyes, and has been shown to induce apoptosis in murine T-lymphoma cells and cardiac fibroblasts. In the brain, CTLA-2 transcript is strongly expressed in neuronal cell bodies while the protein is localized in dendrites and fibre bundles. BCPI has been demonstrated to exhibit anti-parasitic activity and thus thought to act as a negative regulator of silk gland histolysis. Crammer has been identified in mushroom bodies (brain) of Drosophila melanogaster as one of the proteins essential for long-term memory formation through regulation of cathepsin activity in the insect. These findings suggest that the inhibitors are novel proteins that participate in various physiological actions in different organisms. Their emerging roles in normal biological tissues, diseases and as potential targets for drug development are discussed in detail.