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Article type: Research Article
Authors: Pellegrini, Lucaa | Passer, Brent J.a | Canelles, Matildea | Lefterov, Ilyiab | Ganjei, J. Kellya | Fowlkes, B.J.a | Koonin, Eugene V.c | D'Adamio, Lucianoa; *
Affiliations: [a] Laboratory of Cellular and Molecular Immunology, NIH, Bethesda, MD, 20892, USA | [b] Department of Pharmacology, University of Pittsburgh, Pittsburgh, PA, 15261, USA | [c] NCBI, National Library of Medicine, Bethesda, MD, 20892, USA
Correspondence: [*] Corresponding author. Luciano D'Adamio, Albert Einstein College of Medicine, Dept. of Microbiology and Immunology, 1300 Morris Park Avenue, Ullmann, Bronx, NY 10461, USA. Tel.: +1 718 430 3244 12095; Fax: +1 718 430 8711; E-mail: ldadamio@aecom.yu.edu
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.
Keywords: presenilin, AβPP, Alzheimer's disease, Rhomboid, metalloprotease
DOI: 10.3233/JAD-2001-3203
Journal: Journal of Alzheimer's Disease, vol. 3, no. 2, pp. 181-190, 2001
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