Department of Breast Surgery, QiLu Hospital, Jinan, China.
Emergency Department, Shandong Jining No.1 People's Hospital, Jining, China.
PLoS One. 2014 Feb 26;9(2):e90154. doi: 10.1371/journal.pone.0090154. eCollection 2014.
p53 is possibly the most important mammalian tumor suppressor and it is mutated or lost in more than half of all human cancers. The stability of p53 is primarily determined by the RING domain E3 ubiquitin ligase Hdm2, which targets p53 for proteasomal degradation, restraining the potent activity of p53 and enabling cell survival and proliferation. UBE4B has been shown to physically interact with p53 and Hdm2 and to negatively regulate p53 stability and function. However, no one has determined whether UBE4B promotes p53 degradation in breast cancer. In this study, UBE4B promoted the degradation and ubiquitination of p53 to inhibit the apoptosis of cancer cells and promote tumorigenesis. Our results indicate that UBE4B regulates p53 in breast cancer and could be a viable target for developing new therapeutic strategies for breast cancer treatment.
p53 可能是最重要的哺乳动物肿瘤抑制因子，超过一半的人类癌症都存在 p53 突变或缺失。p53 的稳定性主要由 RING 结构域 E3 泛素连接酶 Hdm2 决定，Hdm2 可将 p53 靶向到蛋白酶体进行降解，从而抑制 p53 的有效活性，并使细胞存活和增殖。UBE4B 已被证明与 p53 和 Hdm2 发生物理相互作用，并负调控 p53 的稳定性和功能。然而，目前还没有人确定 UBE4B 是否促进乳腺癌中 p53 的降解。在这项研究中，UBE4B 促进了 p53 的降解和泛素化，从而抑制了癌细胞的凋亡并促进了肿瘤的发生。我们的结果表明，UBE4B 在乳腺癌中调节 p53，因此可能成为开发治疗乳腺癌新的治疗策略的可行靶点。
