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

49 Citations (Scopus)

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
StatePublished - 2001
Externally publishedYes

Fingerprint

Presenilin-2
Presenilins
Presenilin-1
Metalloproteases
Proteins
Membrane Proteins
Peptide Hydrolases
ATP-Dependent Proteases
Notch Receptors
Two-Hybrid System Techniques
Amyloid beta-Protein Precursor
Archaea
Eukaryota
Proteolysis
Alzheimer Disease
Cell Death
Metals
Pathogen-Associated Molecular Pattern Molecules
Bacteria
Amino Acids

Keywords

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

ASJC Scopus subject areas

  • Neuropsychology and Physiological Psychology

Cite this

Pellegrini, L., Passer, B. J., Canelles, M., Lefterov, I., Kelly Ganjei, J., Fowlkes, B. J., ... 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.

PAMP and PARL, two novel putative metalloproteases interacting with the COOH-terminus of Presenilin-1 and -2. / Pellegrini, Luca; Passer, Brent J.; Canelles, Matilde; Lefterov, Ilyia; Kelly Ganjei, J.; Fowlkes, B. J.; Koonin, Eugene V.; D'Adamio, Luciano.

In: Journal of Alzheimer's Disease, Vol. 3, No. 2, 2001, p. 181-190.

Research output: Contribution to journalArticle

Pellegrini, L, Passer, BJ, Canelles, M, Lefterov, I, Kelly Ganjei, J, Fowlkes, BJ, Koonin, EV & 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, vol. 3, no. 2, pp. 181-190.
Pellegrini L, Passer BJ, Canelles M, Lefterov I, Kelly Ganjei J, Fowlkes BJ et al. PAMP and PARL, two novel putative metalloproteases interacting with the COOH-terminus of Presenilin-1 and -2. Journal of Alzheimer's Disease. 2001;3(2):181-190.
Pellegrini, Luca ; Passer, Brent J. ; Canelles, Matilde ; Lefterov, Ilyia ; Kelly Ganjei, J. ; Fowlkes, B. J. ; Koonin, Eugene V. ; D'Adamio, Luciano. / PAMP and PARL, two novel putative metalloproteases interacting with the COOH-terminus of Presenilin-1 and -2. In: Journal of Alzheimer's Disease. 2001 ; Vol. 3, No. 2. pp. 181-190.
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