Gain of function notch phenotypes associated with ectopic expression of the Su(H) C-terminal domain illustrate separability of Notch and hairless-mediated activities.
Gain of function notch phenotypes associated with ectopic expression of the Su(H) C-terminal domain illustrate separability of Notch and hairless-mediated activities.
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DOI：
10.1371/journal.pone.0081578
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Preiss A
中科院分区：
文献类型：
--
作者：
Maier D;Praxenthaler H;Schulz A;Preiss A
Notch信号通路有助于细胞命运的决定。来自Notch受体的信号由CSL型DNA结合蛋白转导。在果蝇中，这种蛋白质被命名为无毛抑制因子[Su（H）]。与活化的Notch受体ICN的胞内结构域一起，Su（H）在Notch靶基因上组装转录激活因子复合物。Hairless是果蝇Notch信号通路的主要拮抗剂，它与Su（H）和几种辅阻遏物形成阻遏复合物。Su（H）的特征在于三个结构域，N-末端结构域NTD、β-三叶结构域BTD和C-末端结构域CTD。NTD和BTD与DNA结合，而BTD和CTD与ICN结合。然而，无毛与CTD结合的位点不同于ICN。在这项工作中，我们已经解决了竞争和可用性的苏（H）的ICN和无毛结合在体内的问题。为此，我们在果蝇发育过程中过表达CTD。我们观察到在各种组织中Notch信号传导过程的强烈激活，这可以通过CTD与无毛辅阻遏物活性的干扰来解释。因此，CTD与Hairless的组合过表达改善了效果，不像Su（H），其在与Hairless同时过表达时强烈增强了阻遏。有趣的是，在组合的过表达中，CTD与无毛一起在细胞核中积累，而其自身主要在细胞质中积累。
The Notch signaling pathway is instrumental for cell fate decisions. Signals from the Notch receptor are transduced by CSL-type DNA-binding proteins. In Drosophila, this protein is named Suppressor of Hairless [Su(H)]. Together with the intracellular domain of the activated Notch receptor ICN, Su(H) assembles a transcriptional activator complex on Notch target genes. Hairless acts as the major antagonist of the Notch signaling pathway in Drosophila by means of the formation of a repressor complex together with Su(H) and several co-repressors. Su(H) is characterized by three domains, the N-terminal domain NTD, the beta-trefoil domain BTD and the C-terminal domain CTD. NTD and BTD bind to the DNA, whereas BTD and CTD bind to ICN. Hairless binds to the CTD, however, to sites different from ICN. In this work, we have addressed the question of competition and availability of Su(H) for ICN and Hairless binding in vivo. To this end, we overexpressed the CTD during fly development. We observed a strong activation of Notch signaling processes in various tissues, which may be explained by an interference of CTD with Hairless corepressor activity. Accordingly, a combined overexpression of CTD together with Hairless ameliorated the effects, unlike Su(H) which strongly enhances repression when overexpressed concomitantly with Hairless. Interestingly, in the combined overexpression CTD accumulated in the nucleus together with Hairless, whereas it is predominantly cytoplasmic on its own.
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DOI：
10.1073/pnas.88.2.632
发表时间：
1991-01-01
影响因子：
11.1
作者：
DECELIS, JF;MARIBEFFA, M;GARCIABELLIDO, A
通讯作者：
GARCIABELLIDO, A
影响因子：
5.3
作者：
Jeffries, S;Robbins, DJ;Capobianco, AJ
通讯作者：
Capobianco, AJ
影响因子：
7.8
作者：
JOHANSEN, KM;FEHON, RG;ARTAVANISTSAKONAS, S
通讯作者：
ARTAVANISTSAKONAS, S
影响因子：
64.8
作者：
JARRIAULT, S;BROU, C;ISRAEL, A
通讯作者：
ISRAEL, A
影响因子：
11.4
作者：
Djiane, Alexandre;Krejci, Alena;Bernard, Frederic;Fexova, Silvie;Millen, Katherine;Bray, Sarah J.
通讯作者：
Bray, Sarah J.