RITA, a novel modulator of Notch signalling, acts via nuclear export of RBP-J
RITA, a novel modulator of Notch signalling, acts via nuclear export of RBP-J
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DOI：
10.1038/emboj.2010.289
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发表时间：
2011-01-05
期刊：
影响因子：
11.4
通讯作者：
Oswald, Franz
中科院分区：
文献类型：
--
作者：
Wacker, Stephan Armin;Alvarado, Cristobal;Oswald, Franz
进化上保守的Notch信号转导途径调节胚胎发育和成年期的基本细胞过程。配体结合诱导受体的早老素依赖性切割和随后的Notch胞内结构域（NICD）的核转位。在细胞核中，NICD与重组信号序列结合蛋白J（RBP-J）/CBF-1转录因子结合以诱导Notch靶基因的表达。在这里，我们报告的RBP-J相互作用和微管蛋白相关（RITA）（C12 ORF 52）作为一种新的RBP-J/CBF-1相互作用蛋白的鉴定和功能特性。RITA是一种高度保守的36 kDa蛋白质，最有趣的是，它与细胞质中的微管蛋白结合，并在细胞质和细胞核之间快速穿梭。这种穿梭RITA从细胞核输出RBP-J/CBF-1。在功能上，我们表明，RITA可以逆转Notch诱导的非洲爪蟾初级神经发生的损失。此外，RITA能够下调Notch介导的转录。因此，我们建议RITA作为Notch信号通路的负调节剂，控制核RBP-J/CBF-1的水平，其量是有限的。The EMBO Journal（2011）30，43-56. doi：10.1038/doj.2010.289; 2010年11月23日在线发布
The evolutionarily conserved Notch signal transduction pathway regulates fundamental cellular processes during embryonic development and in the adult. Ligand binding induces presenilin-dependent cleavage of the receptor and a subsequent nuclear translocation of the Notch intracellular domain (NICD). In the nucleus, NICD binds to the recombination signal sequence-binding protein J (RBP-J)/CBF-1 transcription factor to induce expression of Notch target genes. Here, we report the identification and functional characterization of RBP-J interacting and tubulin associated (RITA) (C12ORF52) as a novel RBP-J/CBF-1-interacting protein. RITA is a highly conserved 36 kDa protein that, most interestingly, binds to tubulin in the cytoplasm and shuttles rapidly between cytoplasm and nucleus. This shuttling RITA exports RBP-J/CBF-1 from the nucleus. Functionally, we show that RITA can reverse a Notch-induced loss of primary neurogenesis in Xenopus laevis. Furthermore, RITA is able to downregulate Notch-mediated transcription. Thus, we propose that RITA acts as a negative modulator of the Notch signalling pathway, controlling the level of nuclear RBP-J/CBF-1, where its amounts are limiting. The EMBO Journal (2011) 30, 43-56. doi:10.1038/emboj.2010.289; Published online 23 November 2010