The Molecular Biology Society of Japan最新文献

{"title":"Structural insights into enzymatic mechanism of methylenetetrahydrofolate reductase (MTHFR) from Sphingobium sp. SYK-6","authors":"Hongyang Yu, N. Kuwabara, T. Senda","doi":"10.1107/S0108767320098475","DOIUrl":"https://doi.org/10.1107/S0108767320098475","url":null,"abstract":"H Yu, N Kamimura, N Kuwabara, R Kato, M Senda, E Masai, T Senda 1 Structural Biology Research Center, Institute of Materials Structure Science, High Energy Accelerator Research Organization (KEK), Tsukuba, Department of Bioengineering, Nagaoka University of Technology, Nagaoka, SBRC, IMSS, KEK, Nagaoka University of Technology, High Energy Accelerator Research Organization (KEK), Tsukuba, Department of Bioengineering, Nagaoka University of Technology, Structural Bio Research Ctr Inst of Materials Structure , High Energy Accelerator Research Org, Tsukuba yuhong@post.kek.jp","PeriodicalId":22984,"journal":{"name":"The Molecular Biology Society of Japan","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84306133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crystal structure of FMN-free form of dihydroorotate dehydrogenase from Trypanosoma brucei .","authors":"T. Kubota, O. Tani, Tomohiko Yamaguchi, I. Namatame, H. Sakashita, K. Furukawa, K. Yamasaki","doi":"10.2210/pdb5xfv/pdb","DOIUrl":"https://doi.org/10.2210/pdb5xfv/pdb","url":null,"abstract":"","PeriodicalId":22984,"journal":{"name":"The Molecular Biology Society of Japan","volume":"2010 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73590822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering the function of KLF4 as a differentiation inducer in haematologic malignancies","authors":"Hiroki Kiyose, K. Morita, Shintaro Maeda, Ken-ichi T. Suzuki, Chieko Tokushige, Yoshimi Yamada, S. Adachi, Yasuhiko Kamikubo","doi":"10.1182/BLOOD.V128.22.1546.1546","DOIUrl":"https://doi.org/10.1182/BLOOD.V128.22.1546.1546","url":null,"abstract":"Kruppel-like factor4 (KLF4) is a member of the KLF family transcription factors, well known for its reprogramming capacities to promote iPS cell transformation. In the context of hematopoietic cells, the major role of KLF4 has attributed to its myeloid to monocyte differentiation capacity and considered to work as a tumor suppressor in acute myeloid leukemia (AML) or myeloid dysplastic syndrome (MDS)-derived cells. Ras-Raf-MEK-ERK pathway is consistently up-regulated in these tumor cells and we have previously reported the role of KLF4 as a major differentiation inducer in this setting, however, how does KLF4 induce monocytic differentiation under MEK-ERK pathway activation has remained unknown. We thus addressed this issue and found a novel key mediator of monocytic differentiation in myeloid leukemia cells. To identify essential downstream factors of KLF4 in myeloid leukemia cells, we first analyzed 3 independent gene expression microarray data sets of AML patients (GSE45194, GSE38810 and GSE22845). AML patients were divided into two groups according to their KLF4 expressions and top 1000 up-regulated genes in KLF4 high-expressing AML patients were extracted. Venn diagram was used to identify the overlapping genes in these data sets and we identified 26 candidate genes possibly involved in KLF4 mediated differentiation in hematologic malignancies. We then performed comprehensive quantitative real-time PCR (qRT-PCR) analysis to examine the expression of all of these candidate genes upon additive KLF4 expression in leukemia cell lines of MOLM-13 and THP-1 cells. Among these genes, KLF4 exceptionally up-regulated the expression of Dihydropyrimidinase like 2 (DPYSL2) over 200-folds. DPYSL2 consists DPYSL gene family. Since previous reports suggest their multiple roles in neuronal differentiation and polarity, as well as in axon growth and guidance, we hereafter focused on this DPYSL2 gene to reveal its veiled function in leukemia cells. Intriguingly, qRT-PCR assay demonstrated that KLF4 uniquely up-regulated the gene expression of DPYSL2 isoform1 among DPYSL family members. We confirmed the specific expression of DPYSL2 isoform1 upon additive KLF4 expression by immunoblotting in AML cells . Chromatin immunoprecipitation (ChIP) assay proved that KLF4 bound directly to the gene promoter region of DPYSL2 isoform1. We next induced the endogenous expression of KLF4 in myeloid leukemia cells using phorbol 12-myristate 13-acetate (PMA) which leads to a rapid and sustained activation of MEK and ERK, ultimately inducing a substantial monocytic differentiation in these cells. PMA treatment induced concomitant expressions of KLF4 and DPYSL2 isoform1 both at mRNA and protein levels in these cells. To assess the function of DPYSL2 isoform1 in myeloid leukemia cells, we generated tetracycline-inducible DPYSL2 isoform1-overexpressing human leukemia cell lines. Upon doxycycline treatment, these leukemia cells differentiated into monocytic lineage with marked CD11b","PeriodicalId":22984,"journal":{"name":"The Molecular Biology Society of Japan","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89387736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of the metabolic and antioxidative effects of taurine, a candidate calorie restriction mimetic compound","authors":"Zi Wang, Yoshihisa Ohata, S. Serizawa, S. Nishizono, T. Chiba","doi":"10.1093/GERONI/IGX004.548","DOIUrl":"https://doi.org/10.1093/GERONI/IGX004.548","url":null,"abstract":"","PeriodicalId":22984,"journal":{"name":"The Molecular Biology Society of Japan","volume":"16 1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74354894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Defining the stem cell lineages in the mouse inter-follicular epidermis","authors":"Aiko Sada, Fadi Jacob, E. Leung, S. Wang, B. S. White, D. Shalloway, T. Tumbar","doi":"10.1016/J.JDERMSCI.2017.02.159","DOIUrl":"https://doi.org/10.1016/J.JDERMSCI.2017.02.159","url":null,"abstract":"","PeriodicalId":22984,"journal":{"name":"The Molecular Biology Society of Japan","volume":"38 1","pages":"195"},"PeriodicalIF":0.0,"publicationDate":"2016-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89985648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Allele-specific ablation rescues electrophysiological abnormalities in human iPS cell model of long-QT syndrome with a CALM2 mutation","authors":"Yuta Yamamoto, T. Makiyama, T. Harita, K. Sasaki, M. Hayano, Suguru Nishiuchi, Yimin Wuriyanghai, H. Kohjitani, Sayako Hirose, Jiarong Chen, T. Ishikawa, S. Ohno, K. Chonabayashi, Y. Yoshida, M. Horie, N. Makita, Takeshi Kimura","doi":"10.14989/doctor.k20673","DOIUrl":"https://doi.org/10.14989/doctor.k20673","url":null,"abstract":"","PeriodicalId":22984,"journal":{"name":"The Molecular Biology Society of Japan","volume":"298 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77764900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell-based Therapy for Parkinson's Disease","authors":"J. Takahashi","doi":"10.1299/JSMEBIO.2018.30.15PM1","DOIUrl":"https://doi.org/10.1299/JSMEBIO.2018.30.15PM1","url":null,"abstract":"","PeriodicalId":22984,"journal":{"name":"The Molecular Biology Society of Japan","volume":"46 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81000009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA methylome analysis in mouse germ cells and early embryos","authors":"Hisato Kobayashi, Tasuku Koike, A. Sakashita, H. Tsuno, Soichiro Kumamoto, T. Wakai, Takashi Sano, T. Kono","doi":"10.26226/morressier.573c1511d462b80296c9845b","DOIUrl":"https://doi.org/10.26226/morressier.573c1511d462b80296c9845b","url":null,"abstract":"","PeriodicalId":22984,"journal":{"name":"The Molecular Biology Society of Japan","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78659353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heterozygous Dnmt3a mutation induces expansion of hematopoietic stem cell pool in a murine model","authors":"T. Higo, J. Koya, Yoshiki Sumitomo, Takako Tsuruta, K. Kataoka, T. Satou, M. Kurokawa","doi":"10.1182/blood.v126.23.2355.2355","DOIUrl":"https://doi.org/10.1182/blood.v126.23.2355.2355","url":null,"abstract":"Somatic mutations in DNMT3A, a member of the DNA methyltransferase family, have been identified in various kinds of hematologic malignancies including acute myeloid leukemia (AML), acute lymphoblastic leukemia, myeloproliferative neoplasms, and aplastic anemia. Especially, in cytogenetically normal AML, DNMT3A mutations are detected in 15-20% of cases and associated with poor prognosis. Approximately 40 to 60% of DNMT3A mutations reside at Arg882 (R882), forming hot spot mutation site, implying gain-of-functional property of the mutation in development of leukemia. So far, a functional role of DNMT3A mutation in leukemogenesis has been investigated by overexpressing DNMT3A R882 mutant or Dnmt3a knockout in murine hematopoietic cells. However, the consequenses of DNMT3A R882 mutant with endogenous expression have been largely unknown. To elucidate this, we generated a novel mouse model for Cre-mediated conditional expression of Dnmt3a R878C mutant (homologous to human R882C) from the endogenous locus of Dnmt3a. For hematopoietic cell-specific mutation in vivo, we crossed these mice with Vav-Cre mice. By analyzing genotypes of offspring derived from the pair of Dnmt3aR878C/wt; Vav-Crewt/wt mice and Dnmt3aR882C/wt; Vav-Cretg/wt mice, it is revealed that mice harboring homozygous mutation of Dnmt3a in hematopoietic cells (DNMT3AR882C/R882C; Vav-Cretg/wt) were not born for now. In contrast, Dnmt3aR882C/wt; Vav-Cretg/wt (hereafter Dnmt3a R878C) mice were normally born and they did not show any hematological or other disorders at least until 40 weeks after birth. Additionally, frequencies of peripheral blood mature cells in each lineage are not altered in Dnmt3a R878C mice compared to Dnmt3awt/wt Vav-Cretg/wt (hereafter control mice). To further investigate the effect of DNMT3A R882 mutation, we sacrificed Dnmt3a R878C and control mice at 8-12 weeks after birth and compared the distribution of hematopoietic cells by using flow cytometry. Although there was no obvious difference in the number of mononuclear cells in the whole bone marrow, we found a significant increase of the frequency of long-term hematopoietic stem cells (defined by CD150+ CD48- Lineage- c-Kit+ Sca-1+) in Dnmt3a R878C mice compared to control mice (0.040% and 0.019%, p = 0.022). The frequencies of other progenitors including short-term hematopoietic stem cells, multipotent progenitors, or Lineage- c-Kit+ Sca-1+ (LSK) cells were not changed between Dnmt3a R878C mice and control mice. Moreover, in order to determine whether DNMT3A mutation leads to a qualitative difference in HSCs, we performed colony forming assay. While control LSK cells could not form colonies at fifth round of replating, Dnmt3a R878C LSK cells could be serially replated up to five passages. Additionally, the numbers of colonies in each round were much higher in Dnmt3a R878C cells compared to control cells, suggesting HSCs with heterozygous Dnmt3a R878C mutation have aberrantly enhanced self-renewal capacity. Current","PeriodicalId":22984,"journal":{"name":"The Molecular Biology Society of Japan","volume":"373 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76610456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}