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MAML1 Enhances the Transcriptional Activity of Runx2 and Plays a Role in Bone Development
http://hdl.handle.net/10069/31490
http://hdl.handle.net/10069/31490a72a63fc-2b67-4387-bb01-af40f1bc5318
名前 / ファイル | ライセンス | アクション |
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PLoSGen9_1003132.pdf (2.1 MB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2013-04-24 | |||||
タイトル | ||||||
タイトル | MAML1 Enhances the Transcriptional Activity of Runx2 and Plays a Role in Bone Development | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
著者 |
Watanabe, Takashi
× Watanabe, Takashi× Oyama, Toshinao× Asada, Maki× Harada, Daisuke× Ito, Yoshiaki× Inagawa, Masayo× Suzuki, Yutaka× Sugano, Sumio× Katsube, Ken-ichi× Karsenty, Gerard× Komori, Toshihisa× Kitagawa, Motoo× Asahara, Hiroshi |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Mastermind-like 1 (MAML1) is a transcriptional co-activator in the Notch signaling pathway. Recently, however, several reports revealed novel and unique roles for MAML1 that are independent of the Notch signaling pathway. We found that MAML1 enhances the transcriptional activity of runt-related transcription factor 2 (Runx2), a transcription factor essential for osteoblastic differentiation and chondrocyte proliferation and maturation. MAML1 significantly enhanced the Runx2-mediated transcription of the p6OSE2-Luc reporter, in which luciferase expression was controlled by six copies of the osteoblast specific element 2 (OSE2) from the Runx2-regulated osteocalcin gene promoter. Interestingly, a deletion mutant of MAML1 lacking the N-terminal Notch-binding domain also enhanced Runx2-mediated transcription. Moreover, inhibition of Notch signaling did not affect the action of MAML1 on Runx2, suggesting that the activation of Runx2 by MAML1 may be caused in a Notch-independent manner. Overexpression of MAML1 transiently enhanced the Runx2-mediated expression of alkaline phosphatase, an early marker of osteoblast differentiation, in the murine pluripotent mesenchymal cell line C3H10T1/2. MAML1-/- embryos at embryonic day 16.5 (E16.5) had shorter bone lengths than wild-type embryos. The area of primary spongiosa of the femoral diaphysis was narrowed. At E14.5, extended zone of collagen type II alpha 1 (Col2a1) and Sox9 expression, markers of chondrocyte differentiation, and decreased zone of collagen type X alpha 1 (Col10a1) expression, a marker of hypertrophic chondrocyte, were observed. These observations suggest that chondrocyte maturation was impaired in MAML1-/- mice. MAML1 enhances the transcriptional activity of Runx2 and plays a role in bone development. | |||||
書誌情報 |
PLoS Genetics 巻 9, 号 1, p. e1003132, 発行日 2013-01-10 |
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出版者 | ||||||
出版者 | Public Library of Science | |||||
EISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 15537404 | |||||
DOI | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1371/journal.pgen.1003132 | |||||
権利 | ||||||
権利情報 | © 2013 Watanabe et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | |||||
著者版フラグ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | PLoS Genetics, 9(1), e1003132; 2013 |