Lack of requirement for presenilin1 in Notch1 signaling

B. E. Berechid, G. Thinakaran, P. C. Wong, S. S. Sisodia, J. S. Nye

Research output: Contribution to journalArticlepeer-review

Abstract

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].

Original languageEnglish (US)
Pages (from-to)1493-1497
Number of pages5
JournalCurrent Biology
Volume9
Issue number24
DOIs
StatePublished - Dec 16 1999

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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