当前位置：
X-MOL 学术
›
Cell Death Dis.
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
p53 β-hydroxybutyrylation attenuates p53 activity.
Cell Death & Disease ( IF 8.1 ) Pub Date : 2019-03-11 , DOI: 10.1038/s41419-019-1463-y Kun Liu 1 , Fangzhou Li 1 , Qianqian Sun 1 , Ning Lin 1 , Haichao Han 1 , Kaiqiang You 2 , Feng Tian 3 , Zebin Mao 1 , Tingting Li 2 , Tanjun Tong 1 , Meiyu Geng 4 , Yingming Zhao 5 , Wei Gu 6 , Wenhui Zhao 1
Cell Death & Disease ( IF 8.1 ) Pub Date : 2019-03-11 , DOI: 10.1038/s41419-019-1463-y Kun Liu 1 , Fangzhou Li 1 , Qianqian Sun 1 , Ning Lin 1 , Haichao Han 1 , Kaiqiang You 2 , Feng Tian 3 , Zebin Mao 1 , Tingting Li 2 , Tanjun Tong 1 , Meiyu Geng 4 , Yingming Zhao 5 , Wei Gu 6 , Wenhui Zhao 1
Affiliation
|
p53 is an essential tumor suppressor, whose activity is finely tuned by the posttranslational modifications. Previous research has reported that β-hydroxybutyrate (BHB) induces β-hydroxybutyrylation (Kbhb), which is a novel histone posttranslational modification. Here we report that p53 is modified by kbhb and that this modification occurs at lysines 120, 319, and 370 of p53. We demonstrate that the level of p53 kbhb is dramatically increased in cultured cells treated with BHB and in thymus tissues of fasted mice, and that CBP catalyze p53 kbhb. We show that p53 kbhb results in lower levels of p53 acetylation and reduced expression of the p53 downstream genes p21 and PUMA, as well as reduced cell growth arrest and apoptosis in cultured cells under p53-activating conditions. Similar results were observed in mouse thymus tissue under starvation conditions, which result in increased concentrations of serum BHB, and in response to genotoxic stress caused by γ-irradiation to activate p53. Our findings thus show that BHB-mediated p53 kbhb is a novel mechanism of p53 activity regulation, which may explain the link between ketone bodies and tumor, and which may provide promising therapeutic target for cancer treatment.
中文翻译：
p53β-羟基丁酰化减弱了p53的活性。
p53是必需的肿瘤抑制因子，其活性可通过翻译后修饰进行微调。先前的研究报道了β-羟基丁酸酯（BHB）诱导β-羟基丁酰化（Kbhb），这是一种新型的组蛋白翻译后修饰。在这里，我们报道p53被kbhb修饰，并且该修饰发生在p53的赖氨酸120、319和370处。我们证明在用BHB处理的培养细胞和禁食小鼠的胸腺组织中，p53 kbhb的水平显着增加，并且CBP催化p53 kbhb。我们显示p53 kbhb导致较低水平的p53乙酰化和p53下游基因p21和PUMA的表达降低，以及在p53激活条件下培养细胞的细胞生长停滞和凋亡减少。在饥饿条件下，在小鼠胸腺组织中观察到了相似的结果，这导致血清BHB浓度增加，并响应由γ辐射激活p53引起的遗传毒性应激。因此，我们的发现表明BHB介导的p53 kbhb是p53活性调节的新机制，这可能解释了酮体与肿瘤之间的联系，并可能为癌症治疗提供有希望的治疗靶点。
更新日期：2019-03-11
中文翻译：
p53β-羟基丁酰化减弱了p53的活性。
p53是必需的肿瘤抑制因子，其活性可通过翻译后修饰进行微调。先前的研究报道了β-羟基丁酸酯（BHB）诱导β-羟基丁酰化（Kbhb），这是一种新型的组蛋白翻译后修饰。在这里，我们报道p53被kbhb修饰，并且该修饰发生在p53的赖氨酸120、319和370处。我们证明在用BHB处理的培养细胞和禁食小鼠的胸腺组织中，p53 kbhb的水平显着增加，并且CBP催化p53 kbhb。我们显示p53 kbhb导致较低水平的p53乙酰化和p53下游基因p21和PUMA的表达降低，以及在p53激活条件下培养细胞的细胞生长停滞和凋亡减少。在饥饿条件下，在小鼠胸腺组织中观察到了相似的结果，这导致血清BHB浓度增加，并响应由γ辐射激活p53引起的遗传毒性应激。因此，我们的发现表明BHB介导的p53 kbhb是p53活性调节的新机制，这可能解释了酮体与肿瘤之间的联系，并可能为癌症治疗提供有希望的治疗靶点。
京公网安备 11010802027423号