NF-κB is involved in the regulation of autophagy in mutant p53 cells in response to ionizing radiation.
NF-κB is involved in the regulation of autophagy in mutant p53 cells in response to ionizing radiation.
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NF-kappa B 参与突变 p53 细胞响应电离辐射的自噬调节
DOI：
10.1038/s41420-021-00533-w
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发表时间：
2021-06-25
影响因子：
7
通讯作者：
Liang Z
中科院分区：
文献类型：
--
作者：
Zhu Y;Zuo W;Shen X;Liu Y;Zhao Y;Xiong Y;Cao H;Wang Y;Liang Z
化学疗法和电离辐射（IR）可以在这里诱导自噬。 -R273H）细胞，该乙酰化参与IR诱导的NF-κB核转运。 IR的水平进一步增加了p53-r273H细胞在IR处理后没有变化。 SN50的核，自噬的水平增加了p65的核易位。 NF-κB。p53-R273H细胞中的p300导致p65表达的抑制作用和自噬的增加。在异种移植肿瘤的小鼠模型和临床肿瘤病理标本中，p53基因，NF-κB和自噬之间的关系进一步分析。实验。我们的发现表明，自噬可能受到p53-R273H细胞的NF-κB，这些发现可能有助于改善与突变体P53-R273H基因相关的治疗策略。诱导自噬。
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.
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