Functional complementation between FADD and RIP1 in embryos and lymphocytes

doi:10.1038/nature09878

科研成果详情

题名	Functional complementation between FADD and RIP1 in embryos and lymphocytes
作者	Zhang, Haibing 1; Zhou, Xiaohui1,3; McQuade, Thomas 2; Li, Jinghe 1; Chan, Francis Ka-Ming 2; Zhang, Jianke 1
发表日期	2011-03-17
发表期刊	Nature 影响因子和分区
语种	英语
原始文献类型	Article
摘要	FADD is a common adaptor shared by several death receptors for signalling apoptosis through recruitment and activation of caspase 8 (refs 1-3). Death receptors are essential for immune homeostasis, but dispensable during embryogenesis. Surprisingly, Fadd -/- mice die in utero and conditional deletion of FADD leads to impaired lymphocyte proliferation. How FADD regulates embryogenesis and lymphocyte responses has been a long-standing enigma. FADD could directly bind to RIP1 (also known as RIPK1), a serine/threonine kinase that mediates both necrosis and NF-κB activation. Here we show that Fadd -/- embryos contain raised levels of RIP1 and exhibit massive necrosis. To investigate a potential in vivo functional interaction between RIP1 and FADD, null alleles of RIP1 were crossed into Fadd -/- mice. Notably, RIP1 deficiency allowed normal embryogenesis of Fadd -/- mice. Conversely, the developmental defect of Rip1 -/- lymphocytes was partially corrected by FADD deletion. Furthermore, RIP1 deficiency fully restored normal proliferation in Fadd -/- T cells but not in Fadd -/- B cells. Fadd -/- Rip1 -/- double-knockout T cells are resistant to death induced by Fas or TNF-α and show reduced NF-κB activity. Therefore, our data demonstrate an unexpected cell-type-specific interplay between FADD and RIP1, which is critical for the regulation of apoptosis and necrosis during embryogenesis and lymphocyte function. © 2011 Macmillan Publishers Limited. All rights reserved.
资助项目	National Cancer Institute[R01CA095454];
ISSN	0028-0836
EISSN	0028-0836
卷号	471 期号:7338 页码:373-377
DOI	10.1038/nature09878
收录类别	SCOPUS
URL	查看原文
PubMed ID	21368761
SCOPUSEID	2-s2.0-79952780505
CNS重要论文	CNS重要论文
自科自定义期刊分类	T1类
通讯作者地址	[Zhang, Jianke]Department of Microbiology and Immunology,Kimmel Cancer Center,Thomas Jefferson University,United States
Scopus学科分类	Multidisciplinary
TOP期刊	TOP期刊
引用统计	被引频次：333[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/97778
专题	温州医科大学
通讯作者	Zhang, Jianke
作者单位	1.Department of Microbiology and Immunology,Kimmel Cancer Center,Thomas Jefferson University,United States; 2.Department of Pathology,University of Massachusetts Medical School,United States; 3.College of Life Science,Wenzhou Medical College,China
推荐引用方式 GB/T 7714	Zhang, Haibing,Zhou, Xiaohui,McQuade, Thomas,et al. Functional complementation between FADD and RIP1 in embryos and lymphocytes[J]. Nature,2011,471(7338):373-377.
APA	Zhang, Haibing, Zhou, Xiaohui, McQuade, Thomas, Li, Jinghe, Chan, Francis Ka-Ming, & Zhang, Jianke. (2011). Functional complementation between FADD and RIP1 in embryos and lymphocytes. Nature, 471(7338), 373-377.
MLA	Zhang, Haibing,et al."Functional complementation between FADD and RIP1 in embryos and lymphocytes".Nature 471.7338(2011):373-377.