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在Notch反应性转录因子CSL中鉴定出一个新的激活结构域。

Identification of a novel activation domain in the Notch-responsive transcription factor CSL.

作者信息

Tang Z, Kadesch T

机构信息

Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6145, USA.

出版信息

Nucleic Acids Res. 2001 Jun 1;29(11):2284-91. doi: 10.1093/nar/29.11.2284.

DOI:10.1093/nar/29.11.2284
PMID:11376147
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC55711/
Abstract

CSL is the primary target of the Notch signaling pathway in mammalian cells. It is a DNA binding protein that generally represses transcription in the absence of Notch signaling and activates transcription upon formation of a ternary complex with NICD, the protease-generated intracellular domain of NOTCH: Previous mapping experiments identified the central third of CSL as both necessary and sufficient for DNA binding and activation by NOTCH: Here we show that CSL promotes transcription in 293T cells in the absence of added NICD and that this activity requires both the central domain plus the C-terminal third of the protein. Evidence is presented that argues against a contribution of endogenous NICD and instead supports the possibility that distinct coactivators may directly stimulate the activity of CSL in a cell type-specific manner. This conclusion supports a recent finding that Drosophila CSL (Suppressor of Hairless) can also mediate transcriptional activation in the absence of NOTCH:

摘要

CSL是哺乳动物细胞中Notch信号通路的主要靶点。它是一种DNA结合蛋白,在没有Notch信号时通常抑制转录,而在与NICD(NOTCH蛋白酶产生的细胞内结构域)形成三元复合物后激活转录:先前的定位实验确定CSL的中间三分之一对于DNA结合和Notch激活是必要且充分的:在这里我们表明,在没有添加NICD的情况下,CSL在293T细胞中促进转录,并且这种活性需要蛋白质的中央结构域加上C端的三分之一。有证据表明内源性NICD没有作用,而是支持不同的共激活因子可能以细胞类型特异性方式直接刺激CSL活性的可能性。这一结论支持了最近的一项发现,即果蝇CSL(无翅抑制因子)在没有Notch的情况下也能介导转录激活。

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本文引用的文献

1
The N- and C-terminal regions of RBP-J interact with the ankyrin repeats of Notch1 RAMIC to activate transcription.RBP-J的N端和C端区域与Notch1 RAMIC的锚蛋白重复序列相互作用以激活转录。
Nucleic Acids Res. 2001 Mar 15;29(6):1373-80. doi: 10.1093/nar/29.6.1373.
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Activation of the Notch-regulated transcription factor CBF1/RBP-Jkappa through the 13SE1A oncoprotein.通过13SE1A癌蛋白激活Notch调节的转录因子CBF1/RBP-Jkappa。
Genes Dev. 2001 Feb 15;15(4):380-5. doi: 10.1101/gad.189301.
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A notch-independent activity of suppressor of hairless is required for normal mechanoreceptor physiology.正常机械感受器生理学需要无毛抑制因子的非 Notch 依赖性活性。
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4
MAML1, a human homologue of Drosophila mastermind, is a transcriptional co-activator for NOTCH receptors.MAML1是果蝇主调控因子的人类同源物,是NOTCH受体的转录共激活因子。
Nat Genet. 2000 Dec;26(4):484-9. doi: 10.1038/82644.
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Signal-dependent nuclear export of a histone deacetylase regulates muscle differentiation.一种组蛋白去乙酰化酶的信号依赖性核输出调节肌肉分化。
Nature. 2000 Nov 2;408(6808):106-11. doi: 10.1038/35040593.
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Mastermind is a putative activator for Notch.主调控分子是Notch的一种假定激活因子。
Curr Biol. 2000 Jun 29;10(13):R471-3. doi: 10.1016/s0960-9822(00)00577-7.
7
A novel proteolytic cleavage involved in Notch signaling: the role of the disintegrin-metalloprotease TACE.Notch信号通路中涉及的一种新型蛋白水解切割:解整合素金属蛋白酶TACE的作用。
Mol Cell. 2000 Feb;5(2):207-16. doi: 10.1016/s1097-2765(00)80417-7.
8
A ligand-induced extracellular cleavage regulates gamma-secretase-like proteolytic activation of Notch1.配体诱导的细胞外切割调节Notch1的γ-分泌酶样蛋白水解激活。
Mol Cell. 2000 Feb;5(2):197-206. doi: 10.1016/s1097-2765(00)80416-5.
9
Regulation of histone deacetylase 4 and 5 and transcriptional activity by 14-3-3-dependent cellular localization.14-3-3依赖的细胞定位对组蛋白去乙酰化酶4和5及转录活性的调控
Proc Natl Acad Sci U S A. 2000 Jul 5;97(14):7835-40. doi: 10.1073/pnas.140199597.
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Functional interaction between the mouse notch1 intracellular region and histone acetyltransferases PCAF and GCN5.小鼠Notch1细胞内区域与组蛋白乙酰转移酶PCAF和GCN5之间的功能相互作用。
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