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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10399714/ https://www.ncbi.nlm.nih.gov/pubmed/36931700 http://dx.doi.org/10.1002/1878-0261.13421 |
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author | Xu, Beihui Li, Qi Zhang, Jianjun Chen, Fuxiang |
author_facet | Xu, Beihui Li, Qi Zhang, Jianjun Chen, Fuxiang |
author_sort | Xu, Beihui |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-10399714 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-103997142023-08-04 LIM domain‐containing protein Ajuba inhibits chemotherapy‐induced apoptosis by negatively regulating p53 stability in colorectal cancer cells Xu, Beihui Li, Qi Zhang, Jianjun Chen, Fuxiang Mol Oncol Research Articles 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. John Wiley and Sons Inc. 2023-04-03 /pmc/articles/PMC10399714/ /pubmed/36931700 http://dx.doi.org/10.1002/1878-0261.13421 Text en © 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Xu, Beihui Li, Qi Zhang, Jianjun Chen, Fuxiang LIM domain‐containing protein Ajuba inhibits chemotherapy‐induced apoptosis by negatively regulating p53 stability in colorectal cancer cells |
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 | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10399714/ https://www.ncbi.nlm.nih.gov/pubmed/36931700 http://dx.doi.org/10.1002/1878-0261.13421 |
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