Study on the putative contribution of caspases and the proteasome to the degradation of Aph-1a and Pen-2

Julie Dunys, Toshitaka Kawarai, Emilie Giaime, Sherwin Wilk, M. Herrant, P. Auberger, Peter St. George-Hyslop, Cristine Alves Da Costa, Frédéric Checler

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

The presenilin-dependent γ-secretase complex is mainly composed of four distinct proteins, namely presenilin 1 or presenilin 2, nicastrin, anterior pharynx defective-1 (Aph-1) and presenilin enhancer (Pen-2). The mechanisms by which the complex is assembled, how its stochiometry is controlled and how its catalytic activity is regulated are poorly understood. Recent studies indicated that Aph-1 and Pen-2 undergo proteolysis by the proteasome. We have examined the susceptibility of endogenous and overexpressed Aph-1a and Pen-2 to proteolysis by endogenous and purified proteasome as well as by recombinant caspases. We show that endogenous Aph-1a and Pen-2 resist proteolysis by caspases and by the proteasome. Furthermore, we show that unexpected interference of proteasome inhibitors with the cmv promoter region driving expression of Aph-1a and Pen-2 led to artifactual enhancement of overexpressed Aph-1a and Pen-2-like immunoreactivities but that these proteins also resist to in vitro degradation by endogenous and purified proteasome.

Original languageEnglish
Pages (from-to)156-163
Number of pages8
JournalNeurodegenerative Diseases
Volume4
Issue number2-3
DOIs
StatePublished - Jun 2007

Keywords

  • Aph-1a
  • Caspase-3
  • Degradation
  • Pen-2
  • Proteasome

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