Kyushu University Academic Staff Educational and Research Activities Database
List of Papers
Eriko Sumiya Last modified date:2021.06.03

Assistant Professor / Research Center for Systems Immunology / Medical Institute of Bioregulation

1. Hiroshi Koyama, Eriko Sumiya, Takahiro Ito, Kazuhisa Sekimizu, Improved method for the PCR-based gene disruption in Saccharomyces cerevisiae, FEMS Yeast Research, 10.1111/j.1567-1364.2007.00334.x, 8, 2, 193-194, 2008.03, The PCR-based gene disruption strategy originally devised by Baudin et al. is widely used for gene targeting in Saccharomyces cerevisiae. An advantage of this strategy is its simplicity in making targeting constructs. The efficiencies of the targeted disruption are highly variable from locus to locus, however, and often very low. In this report, a method for improving the gene deletion efficiency is described..
2. Hiroshi Koyama, Eriko Sumiya, Makiko Nagata, Takahiro Ito, Kazuhisa Sekimizu, Transcriptional repression of the IMD2 gene mediated by the transcriptional co-activator Sub1, Genes to Cells, 10.1111/j.1365-2443.2008.01229.x, 13, 11, 1113-1126, 2008.10, Sub1 was originally identified as a transcriptional co-activator and later demonstrated to have pleiotropic functions during multiple transcription steps, including initiation, elongation and termination. The present study reveals a novel function of Sub1 as a transcription repressor in budding yeast. Sub1 does not activate IMP dehydrogenase 2 (IMD2) gene expression but rather represses its expression. First, we examined the genetic interaction of Sub1 with the transcription elongation factor S-II/TFIIS, which is encoded by the DST1 gene. Disruption of the SUB1 gene partially suppressed sensitivity to the transcription elongation inhibitor mycophenolate (MPA) in a dst1 gene deletion mutant. SUB1 gene deletion increased the expression level of the IMD2 gene, which confers resistance to MPA, indicating that Sub1 functions to repress IMD2 gene expression. Sub1 located around the promoter region of the IMD2 gene. The upstream region of the transcription start sites was required for Sub1 to repress the IMD2 gene expression. These results suggest that the transcriptional co-activator Sub1 also has a role in transcriptional repression during transcription initiation in vivo..
3. K. Tano, H. Hamamoto, T. Ito, Eriko Matsumoto, R. Rakwal, J. Shibato, Y. Masuo, K. Ijiri, K. Sekimizu, N. Akimitsu, Reduced expression of Sytl 1 and Ccdc21 and impaired induction of Mt I by oxidative stress in SII-K1 knockout mice, Drug discoveries & therapeutics, 4, 5, 368-372, 2010.10, SII-K1 is a member of the transcription elongation factor S-II family. In the mouse, SII-K1 is expressed exclusively in the liver, kidney, heart, and skeletal muscle. Here, we report that deletion of the SII-K1 gene in mice resulted in the downregulation of the synaptotagmin-like 1 (Sytl 1) gene in liver and of the coiled-coil domain-containing 21 (Ccdc21) gene in liver and kidney. Moreover, the induction of the metallothionein I (Mt I) gene in SII-K1-deficient mice liver was impaired in diethyl maleate-induced oxidative stress conditions. Our results suggest that SII-K1 regulates these genes in vivo..
4. Yasuhiko Matsumoto, Eriko Sumiya, Takuya Sugita, Kazuhisa Sekimizu, An invertebrate hyperglycemic model for the identification of anti-diabetic drugs, PloS one, 10.1371/journal.pone.0018292, 6, 3, 2011.04, The number of individuals diagnosed with type 2 diabetes mellitus, which is caused by insulin resistance and/or abnormal insulin secretion, is increasing worldwide, creating a strong demand for the development of more effective anti-diabetic drugs. However, animal-based screening for anti-diabetic compounds requires sacrifice of a large number of diabetic animals, which presents issues in terms of animal welfare. Here, we established a method for evaluating the anti-diabetic effects of compounds using an invertebrate animal, the silkworm, Bombyx mori. Sugar levels in silkworm hemolymph increased immediately after feeding silkworms a high glucose-containing diet, resulting in impaired growth. Human insulin and 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR), an AMP-activated protein kinase (AMPK) activator, decreased the hemolymph sugar levels of the hyperglycemic silkworms and restored growth. Treatment of the isolated fat body with human insulin in an in vitro culture system increased total sugar in the fat body and stimulated Akt phosphorylation. These responses were inhibited by wortmannin, an inhibitor of phosphoinositide 3 kinase. Moreover, AICAR stimulated AMPK phosphorylation in the silkworm fat body. Administration of aminoguanidine, a Maillard reaction inhibitor, repressed the accumulation of Maillard reaction products (advanced glycation end-products; AGEs) in the hyperglycemic silkworms and restored growth, suggesting that the growth defect of hyperglycemic silkworms is caused by AGE accumulation in the hemolymph. Furthermore, we identified galactose as a hypoglycemic compound in jiou, an herbal medicine for diabetes, by monitoring its hypoglycemic activity in hyperglycemic silkworms. These results suggest that the hyperglycemic silkworm model is useful for identifying anti-diabetic drugs that show therapeutic effects in mammals..
5. Kaori Tsuji-Takechi, Takako Negishi-Koga, Eriko Sumiyaa, Akiko Kukita, Shigeaki Kato, Takahiro Maeda, Pier Paolo Pandolfi, Keiji Moriyama, Hiroshi Takayanagi, Stage-specific functions of leukemia/lymphoma-related factor (LRF) in the transcriptional control of osteoclast development, Proceedings of the National Academy of Sciences of the United States of America, 10.1073/pnas.1116042109, 109, 7, 2561-2566, 2012.02, Cell fate determination is tightly regulated by transcriptional activators and repressors. Leukemia/lymphoma-related factor (LRF; encoded by Zbtb7a), known as a POK (POZ/BTB and Krüppel) family transcriptional repressor, is induced during the development of bone-resorbing osteoclasts, but the physiological significance of LRF in bone metabolism and the molecular mechanisms underlying the transcriptional regulation of osteoclastogenesis by LRF have not been elucidated. Herewe show that LRF negatively regulates osteoclast differentiation by repressing nuclear factor of activated T cells c1 (NFATc1) induction in the early phase of osteoclast development, while positively regulating osteoclast-specific genes by functioning as a coactivator of NFATc1 in the bone resorption phase. The stage-specific distinct functions of LRF were demonstrated in two lines of conditional knockout mice in which LRF was deleted in the early or late phase of osteoclast development. Thus, this study shows that LRF plays stage-specific distinct roles in osteoclast differentiation, exemplifying the delicate transcriptional regulation at work in lineage commitment..
6. Takako Negishi-Koga, Hans Jürgen Gober, Eriko Sumiya, Noriko Komatsu, Kazuo Okamoto, Shinichiro Sawa, Ayako Suematsu, Tomomi Suda, Kojiro Sato, Toshiyuki Takai, Hiroshi Takayanagi, Immune complexes regulate bone metabolism through FcRγ signalling, Nature communications, 10.1038/ncomms7637, 6, 2015.03, Autoantibody production and immune complex (IC) formation are frequently observed in autoimmune diseases associated with bone loss. However, it has been poorly understood whether ICs regulate bone metabolism directly. Here we show that the level of osteoclastogenesis is determined by the strength of FcRγ signalling, which is dependent on the relative expression of positive and negative FcγRs (FcγRI/III/IV and IIB, respectively) as well as the availability of their ligands, ICs. Under physiological conditions, unexpectedly, FcγRIII inhibits osteoclastogenesis by depriving other osteoclastogenic Ig-like receptors of FcRγ. Fcgr2b-/-mice lose bone upon the onset of a hypergammaglobulinemia or the administration of IgG1 ICs, which act mainly through FcγRIII. The IgG2 IC activates osteoclastogenesis by binding to FcγRI and FcγRIV, which is induced under inflammatory conditions. These results demonstrate a link between the adaptive immunity and bone, suggesting a regulatory role for ICs in bone resorption in general, and not only in inflammatory diseases..
7. Yasuhiko Matsumoto, Masaki Ishii, Yohei Hayashi, Shinya Miyazaki, Takuya Sugita, Eriko Sumiya, Kazuhisa Sekimizu, Diabetic silkworms for evaluation of therapeutically effective drugs against type II diabetes, Scientific reports, 10.1038/srep10722, 5, 2015.05, We previously reported that sugar levels in the silkworm hemolymph, i.e., blood, increase immediately (within 1â €‰h) after intake of a high-glucose diet, and that the administration of human insulin decreases elevated hemolymph sugar levels in silkworms. In this hyperglycemic silkworm model, however, administration of pioglitazone or metformin, drugs used clinically for the treatment of type II diabetes, have no effect. Therefore, here we established a silkworm model of type II diabetes for the evaluation of anti-diabetic drugs such as pioglitazone and metformin. Silkworms fed a high-glucose diet over a long time-period (18â €‰h) exhibited a hyperlipidemic phenotype. In these hyperlipidemic silkworms, phosphorylation of JNK, a stress-responsive protein kinase, was enhanced in the fat body, an organ that functionally resembles the mammalian liver and adipose tissue. Fat bodies isolated from hyperlipidemic silkworms exhibited decreased sensitivity to human insulin. The hyperlipidemic silkworms have impaired glucose tolerance, characterized by high fasting hemolymph sugar levels and higher hemolymph sugar levels in a glucose tolerance test. Administration of pioglitazone or metformin improved the glucose tolerance of the hyperlipidemic silkworms. These findings suggest that the hyperlipidemic silkworms are useful for evaluating the hypoglycemic activities of candidate drugs against type II diabetes..
8. Eriko Sumiya, Takako Negishi-Koga, Yusuke Nagai, Ayako Suematsu, Tomomi Suda, Masahiro Shinohara, Kojiro Sato, Hideki Sanjo, Shizuo Akira, Hiroshi Takayanagi, Phosphoproteomic analysis of kinase-deficient mice reveals multiple TAK1 targets in osteoclast differentiation, Biochemical and Biophysical Research Communications, 10.1016/j.bbrc.2015.06.105, 463, 4, 1284-1290, 2015.08, TAK1 (encoded by Map3k7) is a mitogen-activated protein kinase kinase kinase (MAP3K), which activates the transcription factors AP-1 and NF-κB in response to receptor activator of NF-κB ligand (RANKL) stimulation, thus constituting a key regulator of osteoclast differentiation. Here we report the functional relevance of the kinase activity of TAK1 in the late stage of osteoclast differentiation in vivo using Ctsk-Cre mice and TAK1 mutant mice in which the TAK1 kinase domain was flanked by loxP. The Map3k7flox/kdCtskCre/+ mice displayed a severe osteopetrotic phenotype due to a marked decrease in osteoclast number. RANKL-induced activation of MAPK and NF-κB was impaired in the late stage of osteoclast differentiation. The absence of suppressive effect of an administered NF-κB inhibitor on the late stage of osteoclastogenesis led us to investigate unknown TAK1 targets in osteoclast differentiation. We performed a phosphoproteomic analysis of RANKL-stimulated osteoclast precursor cells from Map3k7flox/kdCtskCre/+ mice, revealing multiple targets regulated by TAK1 during osteoclastogenesis. Thus, TAK1 functions as a critical regulator of the phosophorylation status of various cellular proteins that govern osteoclastogenesis..