LIM domain‐containing protein Ajuba inhibits chemotherapy‐induced apoptosis by negatively regulating p53 stability in colorectal cancer cells
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 func...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-08-01
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| Series: | Molecular Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/1878-0261.13421 |
| _version_ | 1797755328894337024 |
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| author | Beihui Xu Qi Li Jianjun Zhang Fuxiang Chen |
| author_facet | Beihui Xu Qi Li Jianjun Zhang Fuxiang Chen |
| author_sort | Beihui Xu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T17:46:16Z |
| format | Article |
| id | doaj.art-163ce8851b96403aba8d6ffa897d48f4 |
| institution | Directory Open Access Journal |
| issn | 1574-7891 1878-0261 |
| language | English |
| last_indexed | 2024-03-12T17:46:16Z |
| publishDate | 2023-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj.art-163ce8851b96403aba8d6ffa897d48f42023-08-03T16:44:15ZengWileyMolecular Oncology1574-78911878-02612023-08-011781678169110.1002/1878-0261.13421LIM domain‐containing protein Ajuba inhibits chemotherapy‐induced apoptosis by negatively regulating p53 stability in colorectal cancer cellsBeihui Xu0Qi Li1Jianjun Zhang2Fuxiang Chen3Laboratory Medicine, Ninth People's Hospital Shanghai Jiao Tong University School of Medicine ChinaState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica Chinese Academy of Sciences ChinaDepartment of Oral and Maxillofacial‐Head & Neck Oncology, Ninth People's Hospital Shanghai Jiao Tong University School of Medicine ChinaLaboratory Medicine, Ninth People's Hospital Shanghai Jiao Tong University School of Medicine ChinaLIM 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.https://doi.org/10.1002/1878-0261.13421Ajubaapoptosischemoresistancecolorectal cancerp53 |
| spellingShingle | Beihui Xu Qi Li Jianjun Zhang Fuxiang Chen LIM domain‐containing protein Ajuba inhibits chemotherapy‐induced apoptosis by negatively regulating p53 stability in colorectal cancer cells Molecular Oncology Ajuba apoptosis chemoresistance colorectal cancer p53 |
| title | LIM domain‐containing protein Ajuba inhibits chemotherapy‐induced apoptosis by negatively regulating p53 stability in colorectal cancer cells |
| title_full | LIM domain‐containing protein Ajuba inhibits chemotherapy‐induced apoptosis by negatively regulating p53 stability in colorectal cancer cells |
| title_fullStr | LIM domain‐containing protein Ajuba inhibits chemotherapy‐induced apoptosis by negatively regulating p53 stability in colorectal cancer cells |
| title_full_unstemmed | LIM domain‐containing protein Ajuba inhibits chemotherapy‐induced apoptosis by negatively regulating p53 stability in colorectal cancer cells |
| title_short | LIM domain‐containing protein Ajuba inhibits chemotherapy‐induced apoptosis by negatively regulating p53 stability in colorectal cancer cells |
| title_sort | lim domain containing protein ajuba inhibits chemotherapy induced apoptosis by negatively regulating p53 stability in colorectal cancer cells |
| topic | Ajuba apoptosis chemoresistance colorectal cancer p53 |
| url | https://doi.org/10.1002/1878-0261.13421 |
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