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DOI10.1038/ncb1963
Signalling mediated by the endoplasmic reticulum stress transducer OASIS is involved in bone formation
Murakami, Tomohiko1; Saito, Atsushi1; Hino, Shin-ichiro1; Kondo, Shinichi1; Kanemoto, Soshi1; Chihara, Kazuyasu1; Sekiya, Hiroshi1; Tsumagari, Kenji1; Ochiai, Kimiko1; Yoshinaga, Kazuya2; Saitoh, Masahiro3; Nishimura, Riko3; Yoneda, Toshiyuki3; Kou, Ikuyo4; Furuichi, Tatsuya4; Ikegawa, Shiro4; Ikawa, Masahito5,6; Okabe, Masaru5,6; Wanaka, Akio7; Imaizumi, Kazunori1
通讯作者Imaizumi, Kazunori
来源期刊NATURE CELL BIOLOGY
ISSN1465-7392
EISSN1476-4679
出版年2009
卷号11期号:10页码:1205-U90
英文摘要

Eukaryotic cells have signalling pathways from the endoplasmic reticulum (ER) to cytosol and nuclei, to avoid excess accumulation of unfolded proteins in the ER. We previously identified a new type of ER stress transducer, OASIS, a bZIP (basic leucine zipper) transcription factor, which is a member of the CREB/ATF family and has a transmembrane domain(1-6). OASIS is processed by regulated intramembrane proteolysis (RIP) in response to ER stress, and is highly expressed in osteoblasts. OASIS(-/-) mice exhibited severe osteopenia, involving a decrease in type I collagen in the bone matrix and a decline in the activity of osteoblasts, which showed abnormally expanded rough ER, containing of a large amount of bone matrix proteins. Here we identify the gene for type 1 collagen, Col1a1, as a target of OASIS, and demonstrate that OASIS activates the transcription of Col1a1 through an unfolded protein response element (UPRE)-like sequence in the osteoblast-specific Col1a1 promoter region. Moreover, expression of OASIS in osteoblasts is induced by BMP2 (bone morphogenetic protein 2), the signalling of which is required for bone formation. Additionally, RIP of OASIS is accelerated by BMP2 signalling, which causes mild ER stress. Our studies show that OASIS is critical for bone formation through the transcription of Col1a1 and the secretion of bone matrix proteins, and they reveal a new mechanism by which ER stress-induced signalling mediates bone formation.


类型Article
语种英语
国家Japan
收录类别SCI-E
WOS记录号WOS:000270382000009
WOS关键词TRANSCRIPTION FACTOR OASIS ; OSTEOBLAST DIFFERENTIATION ; ER STRESS ; OSTEOGENESIS IMPERFECTA ; COLLAGEN PROMOTER ; CREB/ATF-FAMILY ; TRANSGENIC MICE ; I COLLAGEN ; EXPRESSION ; ASTROCYTES
WOS类目Cell Biology
WOS研究方向Cell Biology
资源类型期刊论文
条目标识符http://119.78.100.177/qdio/handle/2XILL650/162008
作者单位1.Miyazaki Univ, Div Mol & Cellular Biol, Dept Anat, Fac Med, Miyazaki 8891692, Japan;
2.Kumamoto Univ, Sch Hlth Sci, Dept Anat & Pathol, Kumamoto 8620976, Japan;
3.Osaka Univ, Dept Mol & Cellular Biochem, Grad Sch Dent, Suita, Osaka 5650871, Japan;
4.RIKEN SNP Res Ctr, Lab Bone & Joint Dis, Minato Ku, Tokyo 1088639, Japan;
5.Osaka Univ, Genome Informat Res Ctr, Suita, Osaka 5650871, Japan;
6.Osaka Univ, Grad Sch Pharmaceut Sci, Suita, Osaka 5650871, Japan;
7.Nara Med Univ, Dept Anat & Neurosci, Nara 6348521, Japan
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Murakami, Tomohiko,Saito, Atsushi,Hino, Shin-ichiro,et al. Signalling mediated by the endoplasmic reticulum stress transducer OASIS is involved in bone formation[J],2009,11(10):1205-U90.
APA Murakami, Tomohiko.,Saito, Atsushi.,Hino, Shin-ichiro.,Kondo, Shinichi.,Kanemoto, Soshi.,...&Imaizumi, Kazunori.(2009).Signalling mediated by the endoplasmic reticulum stress transducer OASIS is involved in bone formation.NATURE CELL BIOLOGY,11(10),1205-U90.
MLA Murakami, Tomohiko,et al."Signalling mediated by the endoplasmic reticulum stress transducer OASIS is involved in bone formation".NATURE CELL BIOLOGY 11.10(2009):1205-U90.
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