Lack of requirement for Presenilin1 in Notch1 signaling
Lack of requirement for Presenilin1 in Notch1 signaling
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DOI：
10.1016/s0960-9822(00)80121-9
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发表时间：
1999-12-16
期刊：
影响因子：
9.2
通讯作者：
Nye, JS
中科院分区：
文献类型：
--
作者：
Berechid, BE;Thinakaran, G;Nye, JS
Studies in invertebrates have indicated a functional requirement for presenilin (PS) genes in the Notch pathway [1-5], One model of Notch signal transduction suggests that proteolysis releases an activated Notch fragment that migrates to the nucleus and regulates gene transcription in concert with CBF1/Su(H)/lag1 (CSL) proteins [6-9], Recent studies suggest that PS genes control the proteolysis and nuclear access of the Notch intracellular domain [3,4,10,11], offering a basis for the functional interaction of PS and Notch genes [12]. Here, we report that Notch1 signaling elicited by the ligand Delta1 was quantitatively unchanged in PS1-deficient primary embryonic fibroblasts (PEFs), Notch1 signals were measured by both the activation of the hairy/enhancer of split (HES1) promoter and by the antagonism of MyoD-induced muscle creatine kinase (MCK) promoter activity. A membrane-tethered ligand-independent Notch1 construct also showed full efficacy in both assays, despite its presumed requirement for cleavage. Although signaling through Notch1 persisted in PS1 deficient cells, we found a marked reduction in the appearance of a complex of a cleaved, intracellular Notch fragment (NICD) and a CSL protein, as previously reported [6,10]. These studies reveal that PS1 is not required for ligand-dependent Notch signaling, and that PS1 and PS2 may be redundant, Our data also suggest that the identified NICD fragment may not be necessary for Notch signal transduction [9]. (C) 1999 Elsevier Science Ltd. All rights reserved.
