Secrets of a Secretase: N-Cadherin Proteolysis Regulates CBP Function

Presenilin (PS-1) is part of the protease γ-secretase that cleaves the membrane proteins APP and Notch. In this issue of Cell, Marambaud et al. report that PS-1 cleaves the cell adhesion molecule N-cadherin, releasing a C-terminal fragment that promotes degradation of the transcriptional coactivator CBP. Mutations in PS-1 associated with Alzheimerʹs disease interfere with CBP proteolysis, leading to abnormal transcription.