干旱区生态环境知识资源中心(Arid): MBTPS2 mutations cause defective regulated intramembrane proteolysis in X-linked osteogenesis imperfecta

Arid

DOI	10.1038/ncomms11920
	MBTPS2 mutations cause defective regulated intramembrane proteolysis in X-linked osteogenesis imperfecta
	Lindert, Uschi 1,2; Cabral, Wayne A.3; Ausavarat, Surasawadee 4,5,12; Tongkobpetch, Siraprapa 4,5; Ludin, Katja 6; Barnes, Aileen M.3; Yeetong, Patra 4,5,13; Weis, Maryann 7; Krabichler, Birgit 8; Srichomthong, Chalurmpon 4,5; Makareeva, Elena N.9; Janecke, Andreas R.8,10; Leikin, Sergey 9; Rothlisberger, Benno 6; Rohrbach, Marianne 1,2; Kennerknecht, Ingo 11; Eyre, David R.7; Suphapeetiporn, Kanya 4,5; Giunta, Cecilia 1,2; Marini, Joan C.3; Shotelersuk, Vorasuk 4,5
通讯作者	Marini, Joan C.
来源期刊	NATURE COMMUNICATIONS
ISSN	2041-1723
出版年	2016
卷号	7
英文摘要	Osteogenesis imperfecta (OI) is a collagen-related bone dysplasia. We identified an X-linked recessive form of OI caused by defects in MBTPS2, which encodes site-2 metalloprotease (S2P). MBTPS2 missense mutations in two independent kindreds with moderate/severe OI cause substitutions at highly conserved S2P residues. Mutant S2P has normal stability, but impaired functioning in regulated intramembrane proteolysis (RIP) of OASIS, ATF6 and SREBP transcription factors, consistent with decreased proband secretion of type I collagen. Further, hydroxylation of the collagen lysine residue (K87) critical for crosslinking is reduced in proband bone tissue, consistent with decreased lysyl hydroxylase 1 in proband osteoblasts. Reduced collagen crosslinks presumptively undermine bone strength. Also, proband osteoblasts have broadly defective differentiation. These mutations provide evidence that RIP plays a fundamental role in normal bone development.
类型	Article
语种	英语
国家	Switzerland ; USA ; Thailand ; Austria ; Germany
收录类别	SCI-E
WOS记录号	WOS:000380291600001
WOS关键词	ENDOPLASMIC-RETICULUM STRESS ; TRANSCRIPTION FACTORS ; EXTRACELLULAR-MATRIX ; MISSENSE MUTATIONS ; SITE-1 PROTEASE ; BONE-FORMATION ; IFAP SYNDROME ; COLLAGEN ; OASIS ; CLEAVAGE
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/195187
作者单位	1.Univ Childrens Hosp Zurich, Div Metab, Connect Tissue Unit, CH-8032 Zurich, Switzerland; 2.Univ Childrens Hosp Zurich, Childrens Res Ctr, CH-8032 Zurich, Switzerland; 3.NICHHD, Sect Heritable Disorders Bone & Extracellular Mat, NIH, Bethesda, MD 20892 USA; 4.Chulalongkorn Univ, Fac Med, Ctr Excellence Med Genet, Dept Pediat, Bangkok 10330, Thailand; 5.Thai Red Cross Soc, King Chulalongkorn Mem Hosp, Excellence Ctr Med Genet, Bangkok 10330, Thailand; 6.Kantonsspital Aarau, Dept Med Genet, Ctr Lab Med, CH-5001 Aarau, Switzerland; 7.Univ Washington, Dept Orthoped & Sports Med, Seattle, WA 98195 USA; 8.Med Univ Innsbruck, Div Human Genet, A-6020 Innsbruck, Austria; 9.NICHHD, Sect Phys Biochem, NIH, Bethesda, MD 20892 USA; 10.Med Univ Innsbruck, Dept Pediat 1, A-6020 Innsbruck, Austria; 11.Univ Munster, Inst Human Genet, D-48149 Munster, Germany; 12.Mahidol Univ, Siriraj Hosp, Fac Med, Dept Radiol,Div Nucl Med, Bangkok 10700, Thailand; 13.Chulalongkorn Univ, Fac Sci, Dept Bot, Div Human Genet, Bangkok 10330, Thailand
推荐引用方式 GB/T 7714	Lindert, Uschi,Cabral, Wayne A.,Ausavarat, Surasawadee,et al. MBTPS2 mutations cause defective regulated intramembrane proteolysis in X-linked osteogenesis imperfecta[J],2016,7.
APA	Lindert, Uschi.,Cabral, Wayne A..,Ausavarat, Surasawadee.,Tongkobpetch, Siraprapa.,Ludin, Katja.,...&Shotelersuk, Vorasuk.(2016).MBTPS2 mutations cause defective regulated intramembrane proteolysis in X-linked osteogenesis imperfecta.NATURE COMMUNICATIONS,7.
MLA	Lindert, Uschi,et al."MBTPS2 mutations cause defective regulated intramembrane proteolysis in X-linked osteogenesis imperfecta".NATURE COMMUNICATIONS 7(2016).

条目包含的文件
文件名称/大小	资源类型	版本类型	开放类型	使用许可
MBTPS2 mutations cau（1946KB）	期刊论文	出版稿	开放获取	CC BY-NC-SA	浏览