Oue Yuna, Murakami Sara, Isshiki Kinuka, Tsuji Akihiko, Yuasa Keizo
Department of Biological Science and Technology, Tokushima University Graduate School, Minamijosanjima, Tokushima, Japan.
Department of Biological Science and Technology, Tokushima University Graduate School, Minamijosanjima, Tokushima, Japan; Department of Bioscience and Bioindustry, Tokushima University Graduate School, Minamijosanjima, Tokushima, Japan.
Biochem Biophys Res Commun. 2018 Feb 19;496(4):1222-1228. doi: 10.1016/j.bbrc.2018.01.175. Epub 2018 Jan 31.
Death associated protein kinase (DAPK)-related apoptosis-inducing protein kinase (DRAK)-1 is a positive apoptosis regulator. However, the molecular mechanisms underlying the DRAK1-mediated apoptotic pathway remain unclear. In this study, we demonstrated the intracellular localization and binding partners of DRAK1. In human osteosarcoma cell line U2OS cells, DRAK1 was mainly localized in the nucleus and translocated outside the nucleus through Ser phosphorylation by protein kinase C. In the nucleus, DRAK1 associated with tumor suppressor p53 and positively regulated p53 transcriptional activity in response to DNA-damaging agent cisplatin. On the other hand, DRAK1 interacted with the mitochondrial inner-membrane protein, adenine nucleotide translocase (ANT)-2, an anti-apoptotic oncoprotein, outside the nucleus. These findings suggest that DRAK1 translocates in response to stimuli and induces apoptosis through its interaction with specific binding partners, p53 and/or ANT2.
死亡相关蛋白激酶（DAPK）相关凋亡诱导蛋白激酶（DRAK）-1是一种正向凋亡调节因子。然而，DRAK1介导的凋亡途径背后的分子机制仍不清楚。在本研究中，我们展示了DRAK1的细胞内定位和结合伴侣。在人骨肉瘤细胞系U2OS细胞中，DRAK1主要定位于细胞核，并通过蛋白激酶C的丝氨酸磷酸化作用转运至细胞核外。在细胞核内，DRAK1与肿瘤抑制因子p53结合，并在DNA损伤剂顺铂作用下正向调节p53的转录活性。另一方面，在细胞核外，DRAK1与线粒体内膜蛋白腺嘌呤核苷酸转位酶（ANT）-2相互作用，ANT-2是一种抗凋亡癌蛋白。这些发现表明，DRAK1会响应刺激而发生转位，并通过与特定结合伴侣p53和/或ANT2相互作用诱导凋亡。
