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首页> 外文期刊>Molecular cell >GAMT, a p53-inducible modulator of apoptosis, is critical for the adaptive response to nutrient stress.
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GAMT, a p53-inducible modulator of apoptosis, is critical for the adaptive response to nutrient stress.

机译:GAMT是p53诱导的凋亡调节剂,对营养胁迫的适应性反应至关重要。

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摘要

The p53 tumor suppressor protein has a well-established role in cell-fate decision-making processes. However, recent discoveries indicate that p53 has a non-tumor-suppressive role. Here we identify guanidinoacetate methyltransferase (GAMT), an enzyme involved in creatine synthesis, as a p53 target gene and a key downstream effector of adaptive response to nutrient stress. We show that GAMT is not only involved in p53-dependent apoptosis in response to genotoxic stress but is important for apoptosis induced by glucose deprivation. Additionally, p53-->GAMT upregulates fatty acid oxidation (FAO) induced by glucose starvation, utilizing this pathway as an alternate ATP-generating energy source. These results highlight that p53-dependent regulation of GAMT allows cells to maintain energy levels sufficient to undergo apoptosis or survival under conditions of nutrient stress. The p53-->GAMT pathway represents a new link between cellular stress responses and processes of creatine synthesis and FAO, demonstrating a further role of p53 in cellular metabolism.
机译:p53肿瘤抑制蛋白在细胞命运决策过程中具有公认的作用。然而,最近的发现表明p53具有非肿瘤抑制作用。在这里,我们确定胍基乙酸甲酯甲基转移酶(GAMT),一种参与肌酸合成的酶,作为p53靶基因和对营养胁迫适应性反应的关键下游效应子。我们表明,GAMT不仅参与了对基因毒性应激的p53依赖性细胞凋亡,而且对于葡萄糖剥夺诱导的细胞凋亡也很重要。此外,p53-> GAMT利用这种途径作为产生ATP的替代能源,上调了葡萄糖饥饿诱导的脂肪酸氧化(FAO)。这些结果表明,GAMT的p53依赖性调节可使细胞维持足够的能量水平,以在营养胁迫下进行凋亡或存活。 p53-> GAMT途径代表了细胞应激反应与肌酸合成过程和FAO之间的新联系,证明了p53在细胞代谢中的进一步作用。

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