Murine Notch Homologs (N1-4) Undergo Presenilin-dependent Proteolysis

Meera T. Saxena, Eric H. Schroeter, Jeffrey Mumm, Raphael Kopan

Research output: Contribution to journalArticle

Abstract

Oncogenic forms of Notch1, Notch2, and Notch4 appear to mimic signaling intermediates of Notch1 and suggest that the role of proteolysis in Notch signaling has been conserved. Here we demonstrate that extracellularly truncated Notch homologs are substrates for a presenilin-dependent γ-secretase activity. Despite minimal conservation within the transmembrane domain, the requirement for a specific amino acid (P1′ valine) and its position at the cleavage site relative to the cytosolic border of the transmembrane domain are preserved. Cleaved, untethered Notch intracellular domains from each receptor translocate to the nucleus and interact with the transcriptional regulatory protein CSL. All four Notch proteins display presenilin-dependent transactivating potential on a minimal promoter reporter. Thus, this study increases the number of biochemically characterized γ-secretase substrates from two to five. Despite a high degree of structural homology and the presenilin-dependent activity of truncated Notch proteins, the extent that this reflects functional redundancy is unknown.

Original languageEnglish (US)
Pages (from-to)40268-40273
Number of pages6
JournalJournal of Biological Chemistry
Volume276
Issue number43
StatePublished - Oct 26 2001
Externally publishedYes

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Presenilins
Proteolysis
Notch Receptors
Amyloid Precursor Protein Secretases
Valine
Substrates
Redundancy
Conservation
Amino Acids
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

Saxena, M. T., Schroeter, E. H., Mumm, J., & Kopan, R. (2001). Murine Notch Homologs (N1-4) Undergo Presenilin-dependent Proteolysis. Journal of Biological Chemistry, 276(43), 40268-40273.

Murine Notch Homologs (N1-4) Undergo Presenilin-dependent Proteolysis. / Saxena, Meera T.; Schroeter, Eric H.; Mumm, Jeffrey; Kopan, Raphael.

In: Journal of Biological Chemistry, Vol. 276, No. 43, 26.10.2001, p. 40268-40273.

Research output: Contribution to journalArticle

Saxena, MT, Schroeter, EH, Mumm, J & Kopan, R 2001, 'Murine Notch Homologs (N1-4) Undergo Presenilin-dependent Proteolysis', Journal of Biological Chemistry, vol. 276, no. 43, pp. 40268-40273.
Saxena, Meera T. ; Schroeter, Eric H. ; Mumm, Jeffrey ; Kopan, Raphael. / Murine Notch Homologs (N1-4) Undergo Presenilin-dependent Proteolysis. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 43. pp. 40268-40273.
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