{"created":"2023-05-15T09:59:01.737093+00:00","id":3105,"links":{},"metadata":{"_buckets":{"deposit":"58fb639a-807b-4214-8fb9-ddaa017cc10e"},"_deposit":{"created_by":5,"id":"3105","owner":"5","owners":[5],"pid":{"revision_id":0,"type":"depid","value":"3105"},"status":"published"},"_oai":{"id":"oai:miyazaki-u.repo.nii.ac.jp:00003105","sets":["72","72:40"]},"author_link":["16326"],"item_10007_description_13":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"1.t(1;3)転座を有する白血病の責任遺伝子MEL1には未だ不明な点が多い(Mochizuki,2000;Nishikata,2003)。これまでの解析から、MEL1SはCtBPの有無に関わらずHDAC群と相互作用すること、少なくとも一部のHDACはCtBPと相互作用しないことから、MEL1SとHDACの相互作用にはCtBPに替わる新たな因子の関与が示唆され、探索中である。G9Aは転写抑制に関与するメチル化転移酵素で、MEL1が属するPRDMのPRDI-BF1やPRISMとの相互作用が最近報告され、実際にRT-PCR法によりL-G3細胞での発現が確認された。免疫沈降WA法による解析から、MEL1SはG9Aと反応し、CtBP存在下で相互作用はさらに強まったが、CtBP非結合型変異体ASではほとんど反応を認めなかったことから、少なくとも、L-G3細胞での分化誘導阻止に関係する因子ではないことが示唆された。 2.転写因子としての機能を明らかにするため、病態的、構造的、機能的に酷似したEVI1の標的遺伝子GATA-2ISに関するプロモーターアッセイ(Yuasa,2005)を用い、遺伝子産物MEL1SおよびASについて調べた。293TやCOS7、HeLa、CHO細胞の場合、MEL1Sは弱い転写抑制(^~30%)を示すが、ASではほとんど効果が無かった。L-G3の場合、MEL1Sが強い抑制(^~80%)を示し、ASでも効果を認めた(^~45%)。両蛋白質を安定発現させたL-G3細胞でGCSFによる分化誘導が阻止され、これをTSA添加で解除できた(課題番号16590950)ことから、HDAC群のリクルートを介してMEL1SがGATA-2の転写を抑制することがL-G3細胞での分化誘導阻止に関係することが想起されるが、関与する他の因子とその機構については更なる検討が必要である。","subitem_description_language":"ja","subitem_description_type":"Abstract"},{"subitem_description":"The MDS1/EVI1-like gene 1 (MEL1) was identified as transcriptional regulator that was the causative factor in pathogenesis of the t (1 ; 3) (p36 ; q21)-positive acute myeloid leukemia. However, the molecular basis of their transcriptional functions has remained elusive. Recently, we have shown that the ecotropic virus integration site-1 (EVI1) binds to its DNA consensus sequence located around 6-7 kb upstream region of the GATA-2 IS exon and up-regulates the expression of GATA-2 gene in EML-C1, a murine multipotent progenitor cell line (Yuasa, et. al., 2005). In contrast, Overexpression of MEL1S, PR domain-defective short form in L-G3, a IL-3-dependent murine myeloid cell line, blocks G-CSF-induced myeloid differentiation and down-regulate the expression of GATA-2 gene. To determine whether the binding of MEL1S to CtBP is required for action of MEL1S in GATA-2 gene regulation, We created CtBP-binding-deficient mutant of MEL1S (PFAST/PLASS).With the reporter gene containing 0~7 kb upstream region of the GATA-2 IS exon, This wild-type and the mutant of MELlS were ectopically expressed in L-G3 cells as above and 293T, HeLa, COS7, CHO cells, authentic fibroblast cell lines, respectively. When wild-type and the mutant of MEL1S was transiently expressed in L-G3 cells, wild-type MEL1S significantly reduced the activity of GATA-2 IS promoter by 70%, but the repression was greatly reduced in cells expressing mutant MELlS (40% reduction). By the other hand, the activity of GATA-2 IS promoter was not suppressed by the mutant MEL1S that does not bind CtBP in fibroblast cells tested, when wild-type MEL1S slightly reduced by 30%. These findings highlight the relationship between the expression of GATA-2 gene regulated by MEL1S and the interaction of MEL1S and HDAC and how these factors affect the gene expression and leukemogenesis of MEL1S in leukemia cells.","subitem_description_type":"Abstract"}]},"item_10007_description_14":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"平成18年度~平成19年度 科学研究費補助金 \n(基盤研究(C)) \n研究成果報告書","subitem_description_language":"ja","subitem_description_type":"Other"}]},"item_10007_textarea_26":{"attribute_name":"目次情報","attribute_value_mlt":[{"subitem_textarea_language":"ja","subitem_textarea_value":"p1:はしがき\np2:研究組織、交付決定額、研究発表\npp.3-8: 本文\npp.8-9: まとめ、今後の展開\npp.9-11:参考文献\npp.12-23:図版"}]},"item_10007_version_type_20":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2020-06-21"}],"displaytype":"detail","filename":"18591075-1.pdf","filesize":[{"value":"21.6 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"18591075-1.pdf","url":"https://miyazaki-u.repo.nii.ac.jp/record/3105/files/18591075-1.pdf"},"version_id":"fd54bae4-1cfa-437e-9355-fbb7ac18eea3"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2020-06-21"}],"displaytype":"detail","filename":"18591075-2.pdf","filesize":[{"value":"3.4 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"18591075-2.pdf","url":"https://miyazaki-u.repo.nii.ac.jp/record/3105/files/18591075-2.pdf"},"version_id":"adda0570-dfca-4d1f-a28d-fe5e3cecad43"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"白血病, t(1;3)転座, 発現制御, 発症機構","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"leukemogenesis, t(1 : 3) translocation, MEL1 (PRDM16), GATA-2 gene regulation","subitem_subject_language":"en","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"jpn"}]},"item_researcher":{"attribute_name":"研究代表者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"西片, 一朗","creatorNameLang":"ja"},{"creatorName":"ニシカタ, イチロウ","creatorNameLang":"ja-Kana"}],"nameIdentifiers":[{"nameIdentifier":"16326","nameIdentifierScheme":"WEKO"}]}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"research report","resourceuri":"http://purl.org/coar/resource_type/c_18ws"}]},"item_title":"MEL1S-EVI1遺伝子群による白血病発症機構の検討","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"MEL1S-EVI1遺伝子群による白血病発症機構の検討","subitem_title_language":"ja"},{"subitem_title":"analysis of leukemogenesis by MELS in MEL-EVI1 gene family","subitem_title_language":"en"}]},"item_type_id":"10007","owner":"5","path":["72","40"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2012-11-08"},"publish_date":"2012-11-08","publish_status":"0","recid":"3105","relation_version_is_last":true,"title":["MEL1S-EVI1遺伝子群による白血病発症機構の検討"],"weko_creator_id":"5","weko_shared_id":-1},"updated":"2024-01-30T04:27:02.169038+00:00"}