SUMO1-regulated DBC1 promotes p53-dependent stress-induced apoptosis of lens epithelial cells.
SUMO1-regulated DBC1 promotes p53-dependent stress-induced apoptosis of lens epithelial cells.
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DOI：
10.18632/aging.205001
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发表时间：
2023-09-07
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影响因子：
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人乳腺癌基因1（DBC1）最初是从人染色体8p21的一个同源性缺失区域中鉴定出来的。已经确定，DBC1在癌症发展过程中起双重作用。根据生理环境，它可以促进或抑制肿瘤发生。它是否在透镜发病机制中起作用仍然是一个谜。在本研究中，我们证明了DBC 1是高表达的透镜上皮细胞从不同的脊椎动物和视网膜色素上皮细胞以及。此外，在人和小鼠透镜上皮细胞中，DBC 1通过SUMO 1在K591残基处缀合而SUMO化。SUMO化的DBC 1定位于细胞核中，在促进应激诱导的细胞凋亡中起重要作用。沉默的DBC1减弱氧化应激诱导的细胞凋亡。相反，过表达的DBC1增强氧化应激诱导的细胞凋亡，这一过程依赖于p53。在机制上，DBC1与p53相互作用以调节其在多个位点的磷酸化状态，并且DBC1的SUMO化增强其与p53的相互作用。总之，我们的研究结果表明，DBC1是一个重要的调节介导的压力诱导的细胞凋亡的透镜，从而参与控制透镜白内障的发生。
Deleted in breast cancer 1 (DBC1) was initially identified from a homozygously deleted region in human chromosome 8p21. It has been well established that DBC1 plays a dual role during cancer development. Depending on the physiological context, it can promote or inhibit tumorigenesis. Whether it plays a role in lens pathogenesis remains elusive. In the present study, we demonstrated that DBC1 is highly expressed in lens epithelial cells from different vertebrates and in retina pigment epithelial cells as well. Moreover, DBC1 is SUMOylated through SUMO1 conjugation at K591 residue in human and mouse lens epithelial cells. The SUMOylated DBC1 is localized in the nucleus and plays an essential role in promoting stress-induced apoptosis. Silence of DBC1 attenuates oxidative stress-induced apoptosis. In contrast, overexpression of DBC1 enhances oxidative stress-induced apoptosis, and this process depends on p53. Mechanistically, DBC1 interacts with p53 to regulate its phosphorylation status at multiple sites and the SUMOylation of DBC1 enhances its interaction with p53. Together, our results identify that DBC1 is an important regulator mediating stress-induced apoptosis in lens, and thus participates in control of lens cataractogenesis.
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影响因子：
11.8
作者：
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通讯作者：
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影响因子：
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影响因子：
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作者：
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通讯作者：
GLUCKSMANN, A
DOI：
10.1073/pnas.2221522120
发表时间：
2023-08
影响因子：
11.1
作者：
Fu, Jia-Ling;Zheng, Shu-Yu;Wang, Yan;Hu, Xue-Bin;Xiao, Yuan;Wang, Jing-Miao;Zhang, Lan;Wang, Ling;Nie, Qian;Hou, Min;Bai, Yue-Yue;Gan, Yu -Wen;Liang, Xing-Miao;Xie, Liu -Liu;Li, David Wan-Cheng
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