LIM domain-containing protein Ajuba inhibits chemotherapy-induced apoptosis by negatively regulating p53 stability in colorectal cancer cells.
LIM domain-containing protein Ajuba inhibits chemotherapy-induced apoptosis by negatively regulating p53 stability in colorectal cancer cells.
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含LIM结构域的蛋白Ajuba通过负调节结肠直肠癌细胞中p53稳定性来抑制化疗诱导的凋亡
DOI：
10.1002/1878-0261.13421
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发表时间：
2023-08
影响因子：
6.6
通讯作者：
Chen, Fuxiang
中科院分区：
文献类型：
--
作者：
Xu, Beihui;Li, Qi;Zhang, Jianjun;Chen, Fuxiang
含有LIM蛋白结构域的蛋白Ajuba（由AjuBA编码）作为支架蛋白发挥作用，调节蛋白质-蛋白质相互作用，信号转导和基因转录。AJUBA在结直肠癌组织中的表达高于正常组织，但其在结直肠癌进展中的具体分子功能尚不十分清楚。在这里，我们发现，在CRC癌细胞系中，AJUBA的过表达降低了p53水平，而AJUBA的敲低显著增加了p53水平。虽然筋骨草的存在不影响p53的转录，但它与p53和MDM 2形成复合物，以促进p53的降解。AJUBA过表达降低了癌细胞对化疗药物的敏感性，反之亦然。此外，化疗药物显着诱导AJUBA的表达，这在很大程度上依赖于p53的存在。因此，筋骨草形成负反馈回路来调节p53的表达和活性。结论：筋骨草作为一种新型p53负调控因子，能够抑制化疗药物诱导的大肠癌细胞凋亡，有望成为大肠癌治疗的新靶点。筋骨草是一种新型的p53负调控因子，以负反馈方式抑制化疗药物诱导的细胞凋亡。筋骨草直接与p53/MDM 2相互作用，增强p53/MDM 2相互作用，促进p53降解。这些结果表明，Ajuba在大肠癌中的高表达可介导化疗耐药，并且Ajuba可能是大肠癌治疗的潜在靶点。
LIM protein‐domain containing protein Ajuba (encoded by AJUBA) functions as a scaffold protein to regulate protein–protein interactions, signalling transduction and genes transcription. AJUBA expression is higher in colorectal cancer (CRC) tissues than normal tissues, but its specific molecular function in CRC progression is still not very clear. Here, we found that, in CRC cancer cell lines, overexpression of AJUBA decreased p53 levels, whereas knock‐down of AJUBA significantly increased p53 levels. Although the presence of Ajuba did not influence p53 transcription, it formed a complex with p53 and MDM2 to promote the degradation of p53. AJUBA overexpression reduced the sensitivity of cancer cells to chemotherapeutic drugs and vice versa. In addition, chemotherapeutic drugs significantly induced AJUBA expression, which was largely dependent on the presence of p53. Therefore, Ajuba formed a negative feedback loop to regulate p53 expression and activity. In conclusion, as a novel p53‐negative regulator, Ajuba inhibits the apoptosis of CRC cells induced by chemotherapeutic drugs and it may be a new therapeutic target for CRC treatment. Ajuba is a novel negative regulator of p53 and inhibits apoptosis induced by chemotherapy drugs in a negative feedback manner. Ajuba directly interacts with p53/MDM2 and enhances p53/MDM2 interaction and promotes p53 degradation. These results indicate high expression of Ajuba in CRC can mediate chemotherapy resistance, and Ajuba may be a potential therapeutic target for colorectal cancer treatment.
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影响因子：
11.8
作者：
Langer, Ellen M.;Feng, Yunfeng;Longmore, Gregory D.
通讯作者：
Longmore, Gregory D.
p53功能障碍在结直肠癌中的作用及其对治疗的影响。
影响因子：
5.2
作者：
Michel M;Kaps L;Maderer A;Galle PR;Moehler M
通讯作者：
Moehler M
DOI：
10.1016/j.cub.2010.02.035
发表时间：
2010-04-13
期刊：
Current biology : CB
影响因子：
--
作者：
Das Thakur M;Feng Y;Jagannathan R;Seppa MJ;Skeath JB;Longmore GD
通讯作者：
Longmore GD
Ajuba 通过靶向 β-连环蛋白和 YAP 信号传导抑制肝细胞癌细胞生长，并通过 neddylation 受 E3 连接酶 Hakai 调节
DOI：
10.1186/s13046-018-0806-3
发表时间：
2018-07-24
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Liu M;Jiang K;Lin G;Liu P;Yan Y;Ye T;Yao G;Barr MP;Liang D;Wang Y;Gong P;Meng S;Piao H
通讯作者：
Piao H
影响因子：
64.8
作者：
Dornan, D;Wertz, I;Dixit, VM
通讯作者：
Dixit, VM