日本研究人员发现启动变异细胞凋亡的酶
日本研究人员在新一期美国《分子细胞》杂志上发表文章说，他们找到能影响变异细胞凋亡进程的一种酶，如果能加强这种酶的作用，就有望开发出副作用小的癌症新疗法。
细胞中的ＤＮＡ发生变异，细胞就会癌变。在此前的研究中，科学家们发现，细胞中抑制癌变的基因“ｐ５３”会判断ＤＮＡ变异的程度，如果变异较小，这种基因就促使细胞自我修复，若ＤＮＡ变异较大，“ｐ５３”就诱导细胞凋亡。
“ｐ５３”能在某种酶的作用下被激活，但科学家一直未确定是哪种酶。东京医科齿科大学研究人员利用人类癌细胞进行实验时发现，“ＤＹＲＫ２”是激活“ｐ５３”、进而启动细胞凋亡的“开关”。
在实验中，研究人员用药剂使细胞的ＤＮＡ受损，他们观察到“ＤＹＲＫ２”酶从细胞质移动到细胞核，细胞凋亡进程开始。如果人为造成这种酶缺损，细胞凋亡现象就不会发生。
DYRK2 Is Targeted to the Nucleus and Controls p53 via Ser46 Phosphorylation in the Apoptotic Response to DNA Damage
Naoe Taira1, Keishi Nihira1, Tomoko Yamaguchi1, Yoshio Miki1 and Kiyotsugu Yoshida1, 
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1Department of Molecular Genetics, Medical Research Institute, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-ku, Tokyo 113-8510, Japan
Received 29 August 2006; revised 18 December 2006; accepted 2 February 2007. Published: March 8, 2007. Available online 8 March 2007.
Summary
Genotoxic stress exerts biological activity by activating downstream effectors, including the p53 tumor suppressor. p53 regulates cell-cycle checkpoint and induction of apoptosis in response to DNA damage; however, molecular mechanisms responsible for committing to these distinct functions remain to be elucidated. Recent studies demonstrated that phosphorylation of p53 at Ser46 is associated with induction of p53AIP1 expression, resulting in commitment to apoptotic cell death. In this regard, the role for Ser46 kinases in p53-dependent apoptosis has been established; however, the kinases responsible for Ser46 phosphorylation have yet to be identified. Here, we demonstrate that the dual-specificity tyrosine-phosphorylation-regulated kinase 2 (DYRK2) directly phosphorylates p53 at Ser46. Upon exposure to genotoxic stress, DYRK2 translocates into the nucleus for Ser46 phosphorylation. Consistent with these results, DYRK2 induces p53AIP1 expression and apoptosis in a Ser46 phosphorylation-dependent manner. These findings indicate that DYRK2 regulates p53 to induce apoptosis in response to DNA damage.
Author Keywords: SIGNALING; CELLCYCLE
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