Two novel chaperone-like proteins involved in ER quality control mechanism

两种新型伴侣蛋白参与 ER 质量控制机制

基本信息

  • 批准号:
    13308042
  • 负责人:
  • 金额:
    $ 33.95万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (A)
  • 财政年份:
    2001
  • 资助国家:
    日本
  • 起止时间:
    2001 至 2003
  • 项目状态:
    已结题

项目摘要

We found and cloned the gene of a novel stress protein HSP47 which resides in the endoplasmic reticulum (ER) acting as a collagen-specific molecular chaperone in the pathway of collagen biosynthesis, processing and secretion. HSP47 specifically and transiently binds to various types of collagen in the ER. We already succeeded in making knockout mice lacking hsp47 gene, which result in causing the embryonic lethality at 10.5 dpc in hsp47-/-homozygotic mice. In these homozygotic mice, the maturation of type I and type IV collagens was abnormal and the formation of collagen fibrils and basement membranes was impaired suggesting that HSP47 is essential molecular chaperone for collagen.We are also working on ER quality control mechanism, especially on mouse EDEM protein that we have cloned. It is known that misfolded or abnormal proteins accumulated in the ER are retrotranslocated to the cytosol for degradation, and EDEM is expected to play an important role in this process. EDEM recognize only misfolded proteins as substrates in collaboration with calnexin, a molecular chaperone in the ER, and accelerate their degradation. We recently found and cloned the functional homologues of EDEM, soluble EDEM and EDEM3, and now analyzing their functions in ER associated degradation.
我们发现并克隆了一种新的应激蛋白HSP47基因,该蛋白位于内质网(ER)中,在胶原的生物合成、加工和分泌途径中作为胶原特异性分子伴侣。在内质网中,HSP47特异且短暂地与各种类型的胶原蛋白结合。我们已经成功地制造了缺乏hsp47基因的敲除小鼠,导致hsp47-/-纯合子小鼠的胚胎死亡率为10.5 dpc。在这些纯合子小鼠中,I型和IV型胶原成熟异常,胶原原纤维和基底膜的形成受损,表明HSP47是胶原必不可少的分子伴侣。我们也在研究内质网的质量控制机制,特别是我们克隆的小鼠EDEM蛋白。众所周知,内质网中积累的错误折叠或异常蛋白会逆转录到细胞质中进行降解,EDEM有望在这一过程中发挥重要作用。EDEM只识别错误折叠的蛋白质作为底物,与内质网中的分子伴侣钙连联蛋白合作,并加速其降解。我们最近发现并克隆了EDEM、可溶性EDEM和EDEM3的功能同源物,目前正在分析它们在内质网相关降解中的功能。

项目成果

期刊论文数量(32)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
S.OHASHI: "Advanced glycation end products increase collagen-specific chaperone protein in mouse diabetic nephropathy"J.Biol.Chem.. (in press).
S.OHASHI:“高级糖基化终末产物增加小鼠糖尿病肾病中胶原蛋白特异性伴侣蛋白”J.Biol.Chem..(出版中)。
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    0
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  • 通讯作者:
K.NAGATA: "HSP47 as a collagen-specific molecular chaperone : function and expression in normal mouse development"Seminars in Cell and Developmental Biology. 14. 275-282 (2003)
K.NAGATA:“HSP47 作为胶原蛋白特异性分子伴侣:正常小鼠发育中的功能和表达”细胞和发育生物学研讨会。
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    0
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S.MURAKAMI: "Heat shock protein(HSP)47 and collagen are upregulated during neointimal formation in the balloon-injured rat carotid artery"Atherosclerosis. 157. 361-368 (2001)
S.MURAKAMI:“热休克蛋白 (HSP)47 和胶原蛋白在球囊损伤的大鼠颈动脉的新内膜形成过程中上调”动脉粥样硬化。
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    0
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H.YOSHIDA, T.MATSUI, N.HOSOKAWA, R.J.KAUFMAN, K.NAGATA, K.MORI: "A. time-dependent phase shift in the mammalian unfolded proten response"Develop.Cell.. 4(2). 265-271 (2003)
H.YOSHIDA、T.Matsui、N.Hosokawa、R.J.KAUFMAN、K.NAGATA、K.MORI:“哺乳动物未折叠蛋白反应中的时间依赖性相移”Develop.Cell.. 4(2)。
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    0
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M.KIKUCHI: "A single chain Fv fragment 2A3 specific for native lysozyme : Isolation from a human synthetic phage display antibody library and characterization"J. Biochem.. 129. 237-242 (2001)
M.KIKUCHI:“对天然溶菌酶具有特异性的单链 Fv 片段 2A3:从人类合成噬菌体展示抗体库中分离并表征”J.
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NAGATA Kazuhiro其他文献

NAGATA Kazuhiro的其他文献

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{{ truncateString('NAGATA Kazuhiro', 18)}}的其他基金

Mechanism of the maintenance of ER homeostasis by redox regulation
氧化还原调节维持内质网稳态的机制
  • 批准号:
    24227009
  • 财政年份:
    2012
  • 资助金额:
    $ 33.95万
  • 项目类别:
    Grant-in-Aid for Scientific Research (S)
Novel therapeutic strategy of ARDS by the development of Tyrosine kinase PYK2
酪氨酸激酶 PYK2 的开发为 ARDS 提供新的治疗策略
  • 批准号:
    19590906
  • 财政年份:
    2007
  • 资助金额:
    $ 33.95万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Quality control mechanism of misfolded proteins
错误折叠蛋白的质量控制机制
  • 批准号:
    19GS0314
  • 财政年份:
    2007
  • 资助金额:
    $ 33.95万
  • 项目类别:
    Grant-in-Aid for Creative Scientific Research
Quality control mechanism for positive and negative
正反质量控制机制
  • 批准号:
    16207013
  • 财政年份:
    2004
  • 资助金额:
    $ 33.95万
  • 项目类别:
    Grant-in-Aid for Scientific Research (A)
Molecular mechanism of ER-related degradation
ER相关降解的分子机制
  • 批准号:
    14037230
  • 财政年份:
    2002
  • 资助金额:
    $ 33.95万
  • 项目类别:
    Grant-in-Aid for Scientific Research on Priority Areas
Electrochemical reaction of ions in molten slags with electron in thermal plasma
熔渣中的离子与热等离子体中的电子发生电化学反应
  • 批准号:
    11450237
  • 财政年份:
    1999
  • 资助金额:
    $ 33.95万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
New Ironmaking Method at Lower Temperature and Higher Oxygen Potential
低温高氧势炼铁新方法
  • 批准号:
    11355031
  • 财政年份:
    1999
  • 资助金额:
    $ 33.95万
  • 项目类别:
    Grant-in-Aid for Scientific Research (A)
Regulation of cellular Function by molecular chaperones
分子伴侣对细胞功能的调节
  • 批准号:
    09276102
  • 财政年份:
    1997
  • 资助金额:
    $ 33.95万
  • 项目类别:
    Grant-in-Aid for Scientific Research on Priority Areas (A)
Steelmaking Mechanisms for a Tatara Furnace and New Ironmaking
Tatara 炉的炼钢机制和新型炼铁技术
  • 批准号:
    09450277
  • 财政年份:
    1997
  • 资助金额:
    $ 33.95万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Removal of Copper, Zinc and Tin from Iron-based Scraps by Chlorine-Oxygen Gas Mixtures
氯氧混合气体去除铁基废料中的铜、锌和锡
  • 批准号:
    07555227
  • 财政年份:
    1995
  • 资助金额:
    $ 33.95万
  • 项目类别:
    Grant-in-Aid for Scientific Research (A)

相似海外基金

Structural Signatures for Quality Control of Proteins
蛋白质质量控​​制的结构特征
  • 批准号:
    6788602
  • 财政年份:
    2004
  • 资助金额:
    $ 33.95万
  • 项目类别:
Studies of quality control of proteins in the endoplasmic reticulum.
内质网蛋白质质量控​​制的研究。
  • 批准号:
    07308068
  • 财政年份:
    1995
  • 资助金额:
    $ 33.95万
  • 项目类别:
    Grant-in-Aid for Scientific Research (A)
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