Nucleo-cytoplasmic shuttling of murine RBPJ by Hairless protein matches that of Su(H) protein in the model system Drosophila melanogaster.
Nucleo-cytoplasmic shuttling of murine RBPJ by Hairless protein matches that of Su(H) protein in the model system Drosophila melanogaster.
复制标题
DOI：
10.1186/s41065-021-00175-z
复制
发表时间：
2021-03-28
期刊：
影响因子：
2.7
通讯作者：
Nagel AC
中科院分区：
文献类型：
--
作者：
Wolf DB;Maier D;Nagel AC
CSL转录因子在高度保守的Notch信号传导途径中是信号转导的中心。CSL充当分子开关：根据募集的辅因子，CSL诱导Notch靶基因的激活或抑制。出乎意料的是，CSL依赖于它的辅因子进入核，尽管它的作用是基因调控。在果蝇中，CSL同源物无毛抑制子（Su（H））招募无毛（H）进行抑制复合物组装，并最终用于核输入。我们最近发现，Su（H）受到一个动态的核质穿梭，从而严格遵循H亚细胞分布。因此，通过H调节Su（H）的核可用性可能代表Notch信号传导活性的新控制层。在这里，我们扩展了这项工作的小鼠CSL同源RBPJ。使用在内源基因座处携带RBPJwt代替Su（H）的“鼠化”苍蝇模型，我们证明RBPJ蛋白同样遵循H亚细胞分布。例如，核输入缺陷的H* NLS 3蛋白变体的过表达导致RBPJ蛋白的胞质定位，而核输出信号缺陷的H* 内斯蛋白变体的过表达导致RBPJ蛋白在核中的积累。显然，RBPJ也是从细胞核中输出的。总之，这些数据表明，在我们的果蝇模型中，RBPJ与Su（H）一样经历H介导的核质穿梭。这些数据提出了哺乳动物CSL蛋白的核可用性同样受到辅因子限制的可能性，因此可能存在更普遍的调节Notch信号传导活性的模式。
CSL transcription factors are central to signal transduction in the highly conserved Notch signaling pathway. CSL acts as a molecular switch: depending on the cofactors recruited, CSL induces either activation or repression of Notch target genes. Unexpectedly, CSL depends on its cofactors for nuclear entry, despite its role as gene regulator. In Drosophila, the CSL homologue Suppressor of Hairless (Su(H)), recruits Hairless (H) for repressor complex assembly, and eventually for nuclear import. We recently found that Su(H) is subjected to a dynamic nucleo-cytoplasmic shuttling, thereby strictly following H subcellular distribution. Hence, regulation of nuclear availability of Su(H) by H may represent a new layer of control of Notch signaling activity. Here we extended this work on the murine CSL homologue RBPJ. Using a ‘murinized’ fly model bearing RBPJwt in place of Su(H) at the endogenous locus we demonstrate that RBPJ protein likewise follows H subcellular distribution. For example, overexpression of a H*NLS3 protein variant defective of nuclear import resulted in a cytosolic localization of RBPJ protein, whereas the overexpression of a H*NES protein variant defective in the nuclear export signal caused the accumulation of RBPJ protein in the nucleus. Evidently, RBPJ is exported from the nucleus as well. Overall these data demonstrate that in our fly model, RBPJ is subjected to H-mediated nucleo-cytoplasmic shuttling as is Su(H). These data raise the possibility that nuclear availability of mammalian CSL proteins is likewise restricted by cofactors, and may hence present a more general mode of regulating Notch signaling activity.
登录
查看更多内容
影响因子：
4.5
作者：
Praxenthaler H;Nagel AC;Schulz A;Zimmermann M;Meier M;Schmid H;Preiss A;Maier D
通讯作者：
Maier D
影响因子：
9.2
作者：
Roy, S;Shashidhara, LS;VijayRaghavan, K
通讯作者：
VijayRaghavan, K
影响因子：
4
作者：
Nagel, Anja C.;Fischer, Patrick;Preiss, Anette
通讯作者：
Preiss, Anette
影响因子：
2.7
作者：
Maier, Dieter
通讯作者：
Maier, Dieter
影响因子：
2.7
作者：
Brockmann, Birgit;Mastel, Helena;Maier, Dieter
通讯作者：
Maier, Dieter