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P4‐191: PS1 promoter is regulated by methylation
Author(s) -
Fuso Andrea,
Cavallaro Rosaria A.,
Nicolia Vincenzina,
Pasqualato Alessia,
Scarpa Sigfrido
Publication year - 2008
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2008.05.2258
Subject(s) - homocysteine , methylation , dna methylation , vitamin b12 , biology , microbiology and biotechnology , amyloid (mycology) , b vitamins , biochemistry , chemistry , gene , gene expression , endocrinology , botany
changes in the precision of PS/ -secretase have any biological effects. Methods: We used a newly established luciferase reporter assay to evaluate the Notch signaling intensity. The improved construct contains four sequential RBP-J binding sites in the HES-1 promoter region (HES-Y). N-terminal capping antibodies which specifically recognize NICD-S or NICD-V were used to determine S3 cleavage precision. Results: We found that S3 cleavage mediated by PS/ -secretase has diversity, resulting in the production of two types of NICD (NICD-S and NICD-V) with apparently distinct ability to transmit Notch signaling. We also showed that the precision of S3 cleavage can be modulated by physiological factors, which affects the intensity of Notch signaling. Although many PS/ -secretase modifiers have been known to change the precision of -cleavage, it is unknown whether there are any methods which modify the S3 cleavage precision, thus affecting the intensity of Notch signaling. Using the Notch downstream assay and N-terminal capping antibodies which specifically recognize NICD-S or NICD-V, we searched for methods to modify S3 cleavage precision. Conclusions: Pathologically important A 42 upregulating process also exerts physiological function.