PAMP and PARL, two novel putative metalloproteases interacting with the COOH-terminus of Presenilin-1 and -2

Luca Pellegrini, Brent J. Passer, Matilde Canelles, Ilyia Lefterov, J. Kelly Ganjei, B. J. Fowlkes, Eugene V. Koonin, Luciano D'Adamio

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

The familial Alzheimer's disease gene products, presenilin-1 and presenilin-2 (PS1 and PS2), are involved in amyloid β-protein precursor processing (AβPP), Notch receptor signaling, and programmed cell death. However, the molecular mechanisms by which presenilins regulate these processes remain unknown. Clues about the function of a protein can be obtained by seeing whether it interacts with another protein of known function. Using the yeast two-hybrid system, we identified two proteins that interact and colocalize with the presenilins. One of these newly detected presenilin-interacting proteins belongs to the FtsH family of ATP-dependent proteases, and the other one belongs to Rhomboid superfamily of membrane proteins that are highly conserved in eukaryotes, archaea and bacteria. Based on the pattern of amino acid residues conservation in the Rhomboid superfamily, we hypothesize that these proteins possess a metal-dependent enzymatic, possibly protease activity. The two putative proteases interacting with presenilins could mediate specific proteolysis of membrane proteins and contribute to the network of interactions in which presenilins are involved.

Original languageEnglish (US)
Pages (from-to)181-190
Number of pages10
JournalJournal of Alzheimer's Disease
Volume3
Issue number2
DOIs
StatePublished - Jan 1 2001

Keywords

  • Alzheimer's disease
  • AβPP
  • Metalloprotease
  • Presenilin
  • Rhomboid

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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    Pellegrini, L., Passer, B. J., Canelles, M., Lefterov, I., Kelly Ganjei, J., Fowlkes, B. J., Koonin, E. V., & D'Adamio, L. (2001). PAMP and PARL, two novel putative metalloproteases interacting with the COOH-terminus of Presenilin-1 and -2. Journal of Alzheimer's Disease, 3(2), 181-190. https://doi.org/10.3233/JAD-2001-3203