阻断Chk1表达可诱导细胞凋亡并消除G2期检查点机制。
Blocking Chk1 expression induces apoptosis and abrogates the G2 checkpoint mechanism.
作者信息
Luo Y, Rockow-Magnone S K, Kroeger P E, Frost L, Chen Z, Han E K, Ng S C, Simmer R L, Giranda V L
机构信息
Department 47S AP9A, Cancer Research, Pharmaceutical Products Division, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA.
出版信息
Neoplasia. 2001 Sep-Oct;3(5):411-9. doi: 10.1038/sj.neo.7900175.
Checkpoint kinase 1 (Chk1) is a checkpoint gene that is activated after DNA damage. It phosphorylates and inactivates the Cdc2 activating phosphatase Cdc25C. This in turn inactivates Cdc2, which leads to G2/M arrest. We report that blocking Chk1 expression by antisense or ribozymes in mammalian cells induces apoptosis and interferes with the G2/M arrest induced by adriamycin. The Chk1 inhibitor UCN-01 also blocks the G2 arrest after DNA damage and renders cells more susceptible to adriamycin. These results indicate that Chk1 is an essential gene for the checkpoint mechanism during normal cell proliferation as well as in the DNA damage response.
关卡激酶1（Chk1）是一种在DNA损伤后被激活的关卡基因。它使细胞分裂周期蛋白2（Cdc2）激活磷酸酶Cdc25C磷酸化并使其失活。这进而使Cdc2失活，导致G2/M期阻滞。我们报告称，在哺乳动物细胞中通过反义核酸或核酶阻断Chk1表达会诱导细胞凋亡，并干扰阿霉素诱导的G2/M期阻滞。Chk1抑制剂UCN - 01也会阻断DNA损伤后的G2期阻滞，并使细胞对阿霉素更敏感。这些结果表明，Chk1是正常细胞增殖以及DNA损伤反应过程中关卡机制的必需基因。
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