Department of Pharmacology, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
Cancer Lett. 2013 Jun 10;333(2):180-6. doi: 10.1016/j.canlet.2013.01.026. Epub 2013 Jan 22.
DBC1 (deleted in breast cancer 1) participates in the regulation of cell survival and death in response to various stimuli. In particular, DBC1 promotes cell death upon DNA damage through inhibition of SIRT1 deacetylase. However, the SIRT1-independent functions of DBC1 in the regulation of DNA damage response are less well understood. Therefore, we analyzed the DNA damage response in Hs578T breast cancer cell line in which the DBC1-SIRT1 interaction is barely detectable. DBC1-siRNA transfected cells showed a failure in the DNA damage checkpoint and the accumulation of genomic damage following UV irradiation. In addition, DBC1-deficient cells exhibited less JNK activation. Finally, the interruptions of signaling in DBC1-depleted cells contributed to cell death in response to UV irradiation. Overall, these data suggest that DBC1 is essential for a fully efficient and effective response to UV irradiation. Therefore, DBC1 plays a critical role in maintaining genomic stability and cellular integrity following UV-induced genotoxic stress.
DBC1（乳腺癌 1 缺失）参与了对各种刺激的细胞存活和死亡的调节。特别是，DBC1 通过抑制 SIRT1 去乙酰化酶促进 DNA 损伤后的细胞死亡。然而，DBC1 在 DNA 损伤反应调节中的 SIRT1 非依赖性功能尚不清楚。因此，我们分析了 DBC1-SIRT1 相互作用几乎检测不到的 Hs578T 乳腺癌细胞系中的 DNA 损伤反应。用 DBC1-siRNA 转染的细胞在 UV 照射后表现出 DNA 损伤检查点失败和基因组损伤的积累。此外，DBC1 缺陷细胞的 JNK 激活减少。最后，DBC1 耗竭细胞中的信号中断导致对 UV 照射的细胞死亡。总的来说，这些数据表明 DBC1 是对 UV 照射产生完全有效和高效反应所必需的。因此，DBC1 在维持基因组稳定性和细胞完整性方面发挥着关键作用，以应对 UV 诱导的遗传毒性应激。
