Notch and presenilin: a proteolytic mechanism emerges.
Presenilins are needed for proteolytic processing of transmembrane proteins of the Notch/Lin-12 family and for cleavage of the amyloid precursor protein. Accumulating evidence now strongly implicates Presenilin as the catalytic core of a multiprotein complex that executes an unusual intramembranous cleavage of its substrates. In the case of amyloid precursor protein, this cleavage contributes to the generation of small, toxic amyloid peptides that trigger the pathological development of Alzheimer's disease. In the Notch/Lin-12 pathway, Presenilin-mediated cleavage of the receptor is a crucial feature of ligand-induced receptor activation and signal transduction. In this pathway, the Presenilins perform a regulated cleavage event that follows additional processing steps during receptor maturation and ligand-induced ectodomain removal.
Fortini
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Department of Genetics, University of Pennsylvania School of Medicine, Stellar-Chance Laboratories, Room 709C, 422 Curie Boulevard, Philadelphia, Pennsylvania 19104, USA. fortini@mail.med.upenn.edu
D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D029742:Caenorhabditis elegans Proteins; D015801:Helminth Proteins / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism* / Q000502:physiology*; D008954:Models, Biological; D053764:Presenilin-1; D053766:Presenilin-2; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; D015398:Signal Transduction; D014157:Transcription Factors
D016564:Amyloid beta-Protein Precursor; D029742:Caenorhabditis elegans Proteins; D015801:Helminth Proteins; C082460:Lin-12 protein, C elegans; D008565:Membrane Proteins; C497761:NOTCH1 protein, human; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D053764:Presenilin-1; D053766:Presenilin-2; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; D014157:Transcription Factors