Publications

Two 3′ splice variants of the acetylcholine hydrolyzing enzyme acetylcholinesterase (AChE) are expressed in benign and malignant lymphocytes: the major tetrameric AChE-S protein and the stress and disease-inducible monomeric AChE-R. Here, we report that these two proteins play inverse roles in regulating lymphopoiesis through C-terminal interactions with distinct protein partners, so that AChE-S enhances apoptosis of thymocytes, whereas AChE-R promotes their proliferation. Thymocytes from transgenic mice overexpressing AChE-S (TgS) showed increased levels of both AChE-S and the anti-apoptotic AChE-S transcriptional repressor protein partner CtBp, accompanied by decreased CD3+ and CD4+ content, with an outcome of lymphopenia compared to FVB/N controls. Inversely, biopsies from thymomas showed elevated AChE-R and reduced AChE-S and CtBp levels, with suppressed thymocytic apoptosis compared to healthy thymus. Thus, the tumorigenic exchange of AChE-S with AChE-R may facilitate lymphopoiesis in thymoma tumors both because thymocytes lose AChE-S, releasing more CtBp to perform its anti-apoptotic role and since they gain AChE-R, enhancing proliferation.