RIPK1 Blocks Early Postnatal Lethality Mediated by Caspase-8 and RIPK3

被引：564

作者：

Dillon, Christopher P. ^{[1
]}

Weinlich, Ricardo ^{[1
]}

Rodriguez, Diego A. ^{[1
]}

Cripps, James G. ^{[1
]}

Quarato, Giovanni ^{[1
]}

Gurung, Prajwal ^{[1
]}

Verbist, Katherine C. ^{[1
]}

Brewer, Taylor L. ^{[1
]}

Llambi, Fabien ^{[1
]}

Gong, Yi-Nan ^{[1
]}

Janke, Laura J. ^{[2
]}

Kelliher, Michelle A. ^{[3
]}

Kanneganti, Thirumala-Devi ^{[1
]}

Green, Douglas R. ^{[1
]}

机构：

[1] St Jude Childrens Res Hosp, Dept Immunol, Memphis, TN 38105 USA

[2] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA

[3] Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA 01605 USA

来源：

CELL | 2014年 / 157卷 / 05期

基金：

美国国家卫生研究院;

关键词：

DEATH DOMAIN KINASE; NECROSIS-FACTOR RECEPTOR; KAPPA-B ACTIVATION; PROGRAMMED NECROSIS; CELL-DEATH; TNF; UBIQUITINATION; SURVIVAL; INDUCE; FADD;

D O I：

10.1016/j.cell.2014.04.018

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Receptor-interacting protein kinase (RIPK)-1 is involved in RIPK3-dependent and -independent signaling pathways leading to cell death and/or inflammation. Genetic ablation of ripk1 causes postnatal lethality, which was not prevented by deletion of ripk3, caspase-8, or fadd. However, animals that lack RIPK1, RIPK3, and either caspase-8 or FADD survived weaning and matured normally. RIPK1 functions in vitro to limit caspase-8-dependent, TNFR-induced apoptosis, and animals lacking RIPK1, RIPK3, and TNFR1 survive to adulthood. The role of RIPK3 in promoting lethality in ripk1(-/-) mice suggests that RIPK3 activation is inhibited by RIPK1 postbirth. Whereas TNFR-induced RIPK3-dependent necroptosis requires RIPK1, cells lacking RIPK1 were sensitized to necroptosis triggered by poly I: C or interferons. Disruption of TLR (TRIF) or type I interferon (IFNAR) signaling delayed lethality in ripk1(-/-)tnfr1(-/-) mice. These results clarify the complex roles for RIPK1 in postnatal life and provide insights into the regulation of FADD-caspase-8 and RIPK3-MLKL signaling by RIPK1.

引用

页码：1189 / 1202

页数：14

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