Pro-apoptotic protein-protein interactions of the extended N-AChE terminus.
The N-terminally extended "synaptic" acetylcholinesterase variant N-AChE-S operates to promote apoptosis; however, the protein partners involved in this function remain unknown. Here, we report that when microinjected to fertilized mouse oocytes, N-AChE-S caused embryonic death as early as the zygotic stage. To identify the putative protein partners involved, we first tried yeast two hybrid screening, but this approach failed, probably because of the N-AChE-S-induced lethality. In contrast, sequence analysis and a corresponding peptide array revealed possible partners, which were validated by co-immunoprecipitation. These include the kinases GSK3, Aurora and GAK, the membrane integrin receptors, and the death receptor FAS. Each of these could potentially modulate N-AChE-S-induced apoptosis with possible therapeutic value for the treatment of Alzheimer's disease.
Toiber
Debra
D
Department of Biological Chemistry, The Hebrew University of Jerusalem, The Edmond J. Safra Campus, Jerusalem, Israel.
Greenberg
David S
DS
Soreq
Hermona
H
D000110:Acetylcholinesterase / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D064127:Aurora Kinases; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D009410:Nerve Degeneration / Q000378:metabolism* / Q000503:physiopathology; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D020798:Two-Hybrid System Techniques; D019014:fas Receptor / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; D019014:fas Receptor; D064127:Aurora Kinases; C534962:GAK protein, mouse; D017346:Protein Serine-Threonine Kinases; D038362:Glycogen Synthase Kinase 3; D000110:Acetylcholinesterase