A role for cholinesterases in tumorigenesis?
Hydrolysis of the neurotransmitter acetylcholine by acetylcholinesterase (ACHE) and butyrylcholinesterase (BCHE) is the rate-limiting step in the termination of cholinergic signaling at neuromuscular junctions. A growing body of evidence suggests that these enzymes also play a role in tumorigenesis. The ACHE and BCHE genes are amplified, mutated, and/or aberrantly expressed in a variety of human tumor types. These changes could be the result of chromosome breakage, since there is an unusually high frequency of chromosomal abnormalities near the map positions of these genes (3q26-ter and 11p-ter, respectively) in such tumors, particularly hemopoietic malignancies. Both ACHE and BCHE contain the consensus peptide motif S/T-P-X-Z, which is found in many substrates of cdc2-related protein kinases. Here we consider the intriguing possibility that phosphorylation by cdc2-related kinases may be the molecular mechanism linking cholinesterases with tumor cell proliferation. We also discuss the notion that inhibition of these enzymes by commonly used organophosphorous poisons may be tumorigenic in humans.
Soreq
H
H
Department of Biological Chemistry, Life Sciences Institute, Hebrew University of Jerusalem, Israel.
Lapidot-Lifson
Y
Y
Zakut
H
H
D000110:Acetylcholinesterase / Q000235:genetics / Q000502:physiology*; D000595:Amino Acid Sequence; D001932:Brain Neoplasms / Q000139:chemically induced; D002091:Butyrylcholinesterase / Q000235:genetics / Q000502:physiology*; D016203:CDC2 Protein Kinase / Q000502:physiology; D002869:Chromosome Aberrations; D004790:Enzyme Induction; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007938:Leukemia / Q000139:chemically induced; D008954:Models, Biological; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology*; D009369:Neoplasms / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics; D009784:Occupational Diseases / Q000139:chemically induced; D009943:Organophosphorus Compounds / Q000009:adverse effects; D010455:Peptides / Q000737:chemistry; D015398:Signal Transduction; D013379:Substrate Specificity
D009363:Neoplasm Proteins; D009943:Organophosphorus Compounds; D010455:Peptides; D016203:CDC2 Protein Kinase; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase