LIM蛋白结构域含有蛋白Ajuba（由AJUBA编码）作为一个支架蛋白，调节蛋白质相互作用、信号传导和基因转录。与正常组织相比，AJUBA在结直肠癌（CRC）组织中的表达较高，但其在CRC进展中的具体分子功能还不是很清楚。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的敲低则显著增加了p53水平。虽然Ajuba的存在不影响p53的转录，但它与p53和MDM2形成了复合体，促进了p53的降解。AJUBA过表达减少了癌细胞对化疗药物的敏感性，反之亦然。此外，化疗药物显著诱导AJUBA的表达，这在很大程度上取决于p53的存在。因此，Ajuba形成了负反馈回路，调节p53的表达和活性。总之，作为一种新的p53负调节因子，Ajuba抑制了化疗药物诱导的CRC细胞的凋亡，并可能成为CRC治疗的新治疗靶点。本文受版权保护。保留所有权利。

LIM protein-domain containing protein Ajuba (encoded by AJUBA) functions as a scaffold protein to regulate protein-protein interactions, signaling transduction and genes transcription. AJUBA expression is higher in colorectal cancer (CRC) tissues compared with 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 knockdown 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.This article is protected by copyright. All rights reserved.