Laboratory of Cell Biology, Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, 4-20-1 Nasahara, Takatsuki, Osaka, 569-1094, Japan.
Laboratory of Cell Biology, Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, 4-20-1 Nasahara, Takatsuki, Osaka, 569-1094, Japan.
Biochem Biophys Res Commun. 2021 Oct 1;572:65-71. doi: 10.1016/j.bbrc.2021.07.094. Epub 2021 Jul 30.
Previously, we reported that glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is a binding partner of prolyl oligopeptidase (POP) in neuroblastoma NB-1 cells and that the POP inhibitor, SUAM-14746, inhibits cytosine arabinoside (Ara-C)-induced nuclear translocation of GAPDH and protects against Ara-C cytotoxicity. To carry out a more in-depth analysis of the interaction between POP and GAPDH, we generated POP-KO NB-1 cells and compared the nuclear translocation of GAPDH after Ara-C with or without SUAM-14746 treatment to wild-type NB-1 cells by western blotting and fluorescence immunostaining. Ara-C did not induce the nuclear translocation of GAPDH and SUAM-14746 did not protect against Ara-C cytotoxicity in POP-KO cells. These results indicate that the anticancer effects of Ara-C not only include the commonly known antimetabolic effects, but also the induction of cell death by nuclear transfer of GAPDH through interaction with POP.
先前，我们报道了甘油醛-3-磷酸脱氢酶（GAPDH）是神经母细胞瘤 NB-1 细胞中脯氨酰寡肽酶（POP）的结合伴侣，POP 抑制剂 SUAM-14746 可抑制阿糖胞苷（Ara-C）诱导的 GAPDH 核转位，并可抵抗 Ara-C 的细胞毒性。为了对 POP 和 GAPDH 之间的相互作用进行更深入的分析，我们生成了 POP 敲除 NB-1 细胞，并通过 Western blot 和荧光免疫染色比较了 Ara-C 处理或不处理 SUAM-14746 后，野生型 NB-1 细胞中 GAPDH 的核转位。Ara-C 不会诱导 GAPDH 的核转位，而 SUAM-14746 不能保护 POP 敲除细胞免受 Ara-C 的细胞毒性。这些结果表明，Ara-C 的抗癌作用不仅包括常见的抗代谢作用，还包括通过与 POP 相互作用诱导 GAPDH 的核转移导致细胞死亡。
