A novel function of RIP1 in postnatal development and immune homeostasis by protecting against RIP3-dependent necroptosis and FADD-mediated apoptosis.
A novel function of RIP1 in postnatal development and immune homeostasis by protecting against RIP3-dependent necroptosis and FADD-mediated apoptosis.
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DOI：
10.3389/fcell.2015.00012
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发表时间：
2015
影响因子：
5.5
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Dowling JP;Nair A;Zhang J
RIP 1是一种接头激酶，最初被鉴定为能够与TNFR 1和Fas结合，后来被证明参与TLR诱导的信号传导。RIP 1调控的主要信号通路包括坏死性凋亡、凋亡和促存活/炎症NF-κB激活。以往的研究表明，RIP 1缺陷对小鼠胚胎发育没有影响，但会阻碍出生后的发育。这种表型不能很容易地解释，因为缺乏TNFR 1，Fas或TLR的小鼠没有表现出明显的发育缺陷。某些类型的RIP 1缺陷型细胞对TNF诱导的细胞凋亡高度敏感。然而，在我们之前的研究中，细胞凋亡衔接蛋白FADD的缺失对rip 1-/-小鼠的产后发育有轻微的改善。值得注意的是，目前的数据表明，RIP 3（一种已知的坏死性凋亡介质）的单倍体不足使rip 1 −/−fadd−/−小鼠存活超过断奶年龄，尽管由此产生的rip 1 −/−fadd−/− rip 3 +/−小鼠在尺寸和重量上显着较小。此外，完全缺乏RIP 3进一步改善了所产生的rip 1 −/−fadd−/− rip 3 −/−小鼠的出生后发育，这些小鼠显示出正常的大小和体重。在这种三重敲除（TKO）小鼠中，淋巴细胞经历正常发育，但随着小鼠年龄的增长而逐渐积累。然而，TKO小鼠中的这种淋巴组织增生性（lpr）疾病比fadd−/− rip 3 −/−双敲除小鼠的严重程度低。总的来说，数据表明，rip 1 −/−小鼠的出生后发育缺陷部分是由于FADD介导的细胞凋亡以及RIP 3依赖性坏死性凋亡。此外，RIP 1的功能有助于lpr疾病的发展。
RIP1 is an adaptor kinase originally identified as being able to associate with TNFR1 and Fas, and is later shown to be involved in signaling induced by TLRs. Major signaling pathways regulated by RIP1 include necroptosis, apoptosis, and pro-survival/inflammation NF-κB activation. Previous studies show that RIP1 deficiency has no effect on mouse embryogenesis, but blocks postnatal development. This phenotype could not readily be explained, since mice lacking TNFR1, Fas, or TLRs show no apparent developmental defect. Certain types of RIP1-deficient cells are hypersensitive to TNF-induced apoptosis. However, in our previous study, deletion of the apoptotic adaptor protein, FADD, provides marginal improvement of postnatal development of rip1−/− mice. Remarkably, the current data shows that haploid insufficiency of RIP3, a known mediator of necroptosis, allowed survival of rip1−/−fadd−/− mice beyond weaning age, although the resulting rip1−/−fadd−/− rip3+/− mice were significant smaller in size and weight. Moreover, complete absence of RIP3 further improved postnatal development of the resulting rip1−/−fadd−/−rip3−/− mice, which display normal size and weight. In such triple knockout (TKO) mice, lymphocytes underwent normal development, but progressively accumulated as mice age. This lymphoproliferative (lpr) disease in TKO mice is, however, less severe than that of fadd−/−rip3−/− double knockout mice. In total, the data show that the postnatal developmental defect in rip1−/− mice is due in part to FADD-mediated apoptosis as well as RIP3-dependent necroptosis. Moreover, the function of RIP1 contributes to development of lpr diseases.
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DOI：
10.1073/pnas.1102779108
发表时间：
2011-09-13
影响因子：
11.1
作者：
Lu, Jennifer V.;Weist, Brian M.;Walsh, Craig M.
通讯作者：
Walsh, Craig M.
影响因子：
4.8
作者：
Kaiser, William J.;Sridharan, Haripriya;Mocarski, Edward S.
通讯作者：
Mocarski, Edward S.
影响因子：
8.8
作者：
Dillon CP;Oberst A;Weinlich R;Janke LJ;Kang TB;Ben-Moshe T;Mak TW;Wallach D;Green DR
通讯作者：
Green DR
影响因子：
64.5
作者：
Cho YS;Challa S;Moquin D;Genga R;Ray TD;Guildford M;Chan FK
通讯作者：
Chan FK
影响因子：
64.8
作者：
Dannappel M;Vlantis K;Kumari S;Polykratis A;Kim C;Wachsmuth L;Eftychi C;Lin J;Corona T;Hermance N;Zelic M;Kirsch P;Basic M;Bleich A;Kelliher M;Pasparakis M
通讯作者：
Pasparakis M