NF-κB is involved in the regulation of autophagy in mutant p53 cells in response to ionizing radiation
| Autor: | Yan Wang, Wenqing Zuo, Ying Zhu, Yifan Zhao, Yali Liu, Yajie Xiong, Xiao Shen, Zhongqin Liang, Huimin Cao |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cancer Research Immunology Mutant Article 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 0302 clinical medicine Downregulation and upregulation Autophagy Radiosensitivity RC254-282 Cancer Gene knockdown QH573-671 Chemistry Neoplasms. Tumors. Oncology. Including cancer and carcinogens NF-κB Cell Biology In vitro Cell biology 030104 developmental biology Acetylation 030220 oncology & carcinogenesis Cytology |
| Zdroj: | Cell Death Discovery, Vol 7, Iss 1, Pp 1-11 (2021) Cell Death Discovery |
| ISSN: | 2058-7716 |
| Popis: | Chemotherapy and ionizing radiation (IR) can induce autophagy in tumor cells. Here, we report that the level of autophagy in tumor cells was related to the background of p53 gene that NF-κB acts as a negative regulator of autophagy in mutant p53 (p53-R273H) cells, and that acetylation was involved in the IR-induced nuclear translocation of NF-κB. We found that autophagy-related proteins were highly expressed in wild-type p53 (wt-p53) cells and that IR increased their levels further. p53-R273H cells exhibited low levels of autophagy; there was no change following IR treatment. The nuclear translocation of p65 was upregulated in p53-R273H cells following IR; when p65 was competitively inhibited from entering the nucleus with SN50, the level of autophagy increased. The nuclear translocation of p65 was mediated by p300; this factor also regulates the nuclear behavior of NF-κB. The knockdown of p300 in p53-R273H cells led to an inhibition of p65 expression and an increase in autophagy. In addition, the inhibition of p300 or p65 not only activated autophagy, it also induced radiosensitivity in p53-R273H cells. The relationship between the p53 gene, NF-κB, and autophagy was further analyzed in a mouse model of xenograft tumors and in clinical tumor pathological specimens; the results were consistent with the in vitro experiments. Our findings indicate that autophagy may be regulated by NF-κB in p53-R273H cells. These findings may help to improve the therapeutic strategy adopted for tumors related to the mutant p53-R273H gene; such therapy would aim to target NF-κB to induce autophagy. |
| Databáze: | OpenAIRE |
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