The UbL-UBA Ubiquilin4 protein functions as a tumor suppressor in gastric cancer by p53-dependent and p53-independent regulation of p21.
The UbL-UBA Ubiquilin4 protein functions as a tumor suppressor in gastric cancer by p53-dependent and p53-independent regulation of p21.
复制标题
UbL-UBA Ubiquilin4 蛋白通过 p53 依赖性和 p53 独立的 p21 调节发挥胃癌肿瘤抑制因子的作用
DOI：
10.1038/s41418-018-0141-4
复制
发表时间：
2019-03
影响因子：
12.4
通讯作者：
Huang C
中科院分区：
文献类型：
--
作者：
Huang S;Li Y;Yuan X;Zhao M;Wang J;Li Y;Li Y;Lin H;Zhang Q;Wang W;Li D;Dong X;Li L;Liu M;Huang W;Huang C
Ubiquilin 4（Ubqln 4）是UbL-UBA蛋白家族的成员，在通过蛋白酶体途径降解特定底物中充当衔接子。然而，Ubqln 4的生物学功能在很大程度上仍然未知，特别是在癌症中。在此，我们报道了Ubqln 4在胃癌组织中下调，并通过抑制体内和体外胃癌细胞增殖而发挥肿瘤抑制剂的作用。Ubqln 4过表达可诱导胃癌细胞衰老和G1-S期细胞阻滞，并激活p53/p21轴。Ubqln 4通过p53依赖和非p53依赖两种方式调节p21。Ubqln 4与p21的E3泛素连接酶RNF 114相互作用，并负调控其表达水平，这反过来又通过减弱p21的蛋白酶体降解来稳定p21。Ubqln 4的这些作用在p21沉默后的胃癌细胞中部分被废除。我们的研究结果不仅确立了Ubqln 4在胃癌中的抗肿瘤潜力，而且还揭示了Ubqln 4通过稳定p21在调节细胞周期和细胞衰老中的作用。
Ubiquilin4 (Ubqln4), a member of the UbL-UBA protein family, serves as an adaptor in the degradation of specific substrates via the proteasomal pathway. However, the biological function of Ubqln4 remains largely unknown, especially in cancer. Here, we reported that Ubqln4 was downregulated in gastric cancer tissues and functioned as a tumor suppressor by inhibiting gastric cancer cell proliferation in vivo and in vitro. Overexpression of Ubqln4-induced cellular senescence and G1-S cell cycle arrest in gastric cancer cells and activated the p53/p21 axis. Moreover, Ubqln4 regulated p21 through both p53-dependent and p53-independent manners. Ubqln4 interacted with RNF114, an E3 ubiquitin ligase of p21, and negatively regulated its expression level, which in turn stabilized p21 by attenuating proteasomal degradation of p21. These effects of Ubqln4 were partly abrogated in gastric cancer cells upon silencing of p21. Our findings not only establish the anti-tumor potential of Ubqln4 in gastric cancer but also reveal a role for Ubqln4 in regulation of the cell cycle and cellular senescence via stabilizing p21.
登录
查看更多内容
影响因子：
16
作者：
Kleijnen, MF;Shih, AH;Howley, PM
通讯作者：
Howley, PM
ROC1/RBX1 E3泛素连接酶沉默通过顺序诱导G2-M停滞，凋亡和衰老来抑制肿瘤细胞的生长。
影响因子：
11.2
作者：
Jia, Lijun;Soengas, Maria S.;Sun, Yi
通讯作者：
Sun, Yi
影响因子：
4.3
作者：
Chang, Li-Ju;Eastman, Alan
通讯作者：
Eastman, Alan
影响因子：
16
作者：
Jascur, T;Brickner, H;Fotedar, A
通讯作者：
Fotedar, A
影响因子：
8
作者：
Chang, BD;Xuan, YZ;Roninson, IB
通讯作者：
Roninson, IB