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学科主题: 临床医学
题名:
Cytosolic carboxypeptidase CCP6 is required for megakaryopoiesis by modulating Mad2 polyglutamylation
作者: Ye, Buqing1; Li, Chong1; Yang, Zhao1,6; Wang, Yanying1; Hao, Junfeng2; Wang, Li1; Li, Yi7; Du, Ying1; Hao, Lu1; Liu, Benyu1; Wang, Shuo1; Xia, Pengyan1; Huang, Guanling1; Sun, Lei3; Tian, Yong4,5; Fan, Zusen1
刊名: JOURNAL OF EXPERIMENTAL MEDICINE
发表日期: 2014-11-17
DOI: 10.1084/jem.20141123
卷: 211, 期:12, 页:2439-2454
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Immunology ; Medicine, Research & Experimental
研究领域[WOS]: Immunology ; Research & Experimental Medicine
关键词[WOS]: SPINDLE ASSEMBLY CHECKPOINT ; HEMATOPOIETIC STEM-CELLS ; AURORA-B KINASE ; MEGAKARYOCYTE DEVELOPMENT ; ALPHA-TUBULIN ; PLATELET FORMATION ; MAMMALIAN-CELLS ; BETA-TUBULIN ; MICE ; POLYPLOIDIZATION
英文摘要:

Bone marrow progenitor cells develop into mature megakaryocytes (MKs) to produce platelets for hemostasis and other physiological functions. However, the molecular mechanisms underlying megakaryopoiesis are not completely defined. We show that cytosolic carboxy-peptidase (CCP) 6 deficiency in mice causes enlarged spleens and increased platelet counts with underdeveloped MKs and dysfunctional platelets. The prominent phenotypes of CCP6 deficiency are different from those of CCP1-deficient mice. We found that CCP6 and tubulin tyrosine ligase-like family (TTLL) members TTLL4 and TTLL6 are highly expressed in MKs. We identify Mad2 (mitotic arrest deficient 2) as a novel substrate for CCP6 and not CCP1. Mad2 can be polyglutamylated by TTLL4 and TTLL6 to modulate the maturation of MKs. CCP6 deficiency causes hyperglutamylation of Mad2 to promote activation of Aurora B, leading to suppression of MK maturation. We reveal that Mad2 polyglutamylation plays a critical role in the regulation of megakaryopoiesis.

语种: 英语
所属项目编号: XDA01010407 ; XDA01020203 ; 81330047 ; 30830030 ; 31372404 ; 2010CB911902 ; 2014CB964601 ; 20110490617 ; 2012T50145
项目资助者: Chinese Academy of Sciences ; National Natural Science Foundation of China ; National Key Basic Research Program of China ; Chinese Academy of Sciences ; China Postdoctoral Science Foundation
WOS记录号: WOS:000345268800015
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内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/65044
Appears in Collections:北京大学第三临床医学院_麻醉科_期刊论文

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作者单位: 1.Chinese Acad Sci, Inst Biophys, Key Lab Infect & Immun, Beijing 100101, Peoples R China
2.Chinese Acad Sci, Inst Biophys, Lab Anim Res Ctr, Beijing 100101, Peoples R China
3.Chinese Acad Sci, Inst Biophys, Ctr Biol Imaging, Beijing 100101, Peoples R China
4.Chinese Acad Sci, Inst Biophys, Key Lab RNA Biol, Beijing 100101, Peoples R China
5.Chinese Acad Sci, Inst Biophys, Beijing Noncoding RNA Lab, Beijing 100101, Peoples R China
6.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
7.Peking Univ, Hosp 3, Dept Anesthesiol, Beijing 100191, Peoples R China

Recommended Citation:
Ye, Buqing,Li, Chong,Yang, Zhao,et al. Cytosolic carboxypeptidase CCP6 is required for megakaryopoiesis by modulating Mad2 polyglutamylation[J]. JOURNAL OF EXPERIMENTAL MEDICINE,2014,211(12):2439-2454.
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