Fisher David I, McLennan Alexander G
Cell Regulation and Signalling Group, School of Biological Sciences, University of Liverpool, Liverpool L69 7ZB, UK.
Cancer Lett. 2008 Feb 8;259(2):186-91. doi: 10.1016/j.canlet.2007.10.007. Epub 2007 Nov 19.
The pro-apoptotic Fhit tumor suppressor protein binds and hydrolyses diadenosine triphosphate (Ap3A) and diadenosine tetraphosphate (Ap4A) in vitro. We have measured the level of both these nucleotides in Fhit-positive HEK293 cells exposed to various apoptosis inducers. Cold shock, anti-Fas, cadmium ions and etoposide all increased the basal level of Ap4A of 0.500pmol/10(6)cells by about 50%. However, the corresponding increases in Ap3A from a basal 0.079pmol/10(6)cells correlated closely with the degree of apoptosis produced, up to a maximum of 0.510pmol/10(6)cells with etoposide. These results support the view that Ap3A is the in vivo Fhit ligand and that an inhibition of Fhit activity is a key element in Fhit-mediated apoptosis.
促凋亡的Fhit肿瘤抑制蛋白在体外能结合并水解三磷酸二腺苷（Ap3A）和四磷酸二腺苷（Ap4A）。我们已测定了暴露于各种凋亡诱导剂的Fhit阳性HEK293细胞中这两种核苷酸的水平。冷休克、抗Fas、镉离子和依托泊苷均使0.500pmol/10⁶细胞的Ap4A基础水平提高了约50%。然而，Ap3A从基础的0.079pmol/10⁶细胞开始的相应增加与所产生的凋亡程度密切相关，依托泊苷处理时最高可达0.510pmol/10⁶细胞。这些结果支持以下观点：Ap3A是Fhit在体内的配体，并且Fhit活性的抑制是Fhit介导的凋亡中的关键因素。
