TY - JOUR
T1 - Pro-apoptotic protein-protein interactions of the extended N-AChE terminus
AU - Toiber, Debra
AU - Greenberg, David S.
AU - Soreq, Hermona
PY - 2009/11
Y1 - 2009/11
N2 - 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.
AB - 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.
KW - Acetylcholinesterase
KW - Apoptosis, N-AChE-S
KW - Neurodegeneration
KW - Protein-protein interactions
UR - http://www.scopus.com/inward/record.url?scp=70449532373&partnerID=8YFLogxK
U2 - 10.1007/s00702-009-0249-2
DO - 10.1007/s00702-009-0249-2
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C2 - 19533292
AN - SCOPUS:70449532373
SN - 0300-9564
VL - 116
SP - 1435
EP - 1442
JO - Journal of Neural Transmission
JF - Journal of Neural Transmission
IS - 11
ER -