p53可抑制戊糖磷酸途径（pentosephosphate-河南师范大学.ppt

* We next investigated whether p53 interacts with G6PD. * Flag-tagged p53 specifically associated with enhanced green fluorescent protein (eGFP) G6PD in vivo. Similarly, endogenous p53 interacted with endogenous G6PD. This interaction was enhanced when cells were treated with the proteasome inhibitor MG132 doxorubicin, both of which stabilized p53. * G6PD is a cytoplasmic protein, whereas p53 is present in both the cytoplasm and the nucleus, and consistently, the p53 - G6PD interaction occurred in the cytoplasm. 谢 谢 聆 听 * * 梁俊平 河南师范大学水产学院 水产动物营养与饲料研究室 p53 regulates biosynthesis through direct inactivation of glucose-6-phosphate dehydrogenase p53 通过直接抑制葡萄糖-6-磷酸脱氢酶活性调控细胞生物合成 * IF 19.679 Abstract Cancer cells consume large quantities of glucose and primarily use glycolysis for ATP production, even in the presence of adequate oxygen. This metabolic signature (aerobic glycolysis or the Warburg effect) enables cancer cells to direct glucose to biosynthesis, supporting their rapid growth and proliferation. 癌细胞生长需要消耗大量葡萄糖，主要是通过糖酵解产生ATP，但这种糖酵解甚至在氧充足条件下依然很活跃。有氧酵解或瓦博格效应的这种代谢特征促进了癌细胞直接将葡萄糖进行生物合成，维持癌细胞快速、无限增殖。 * 糖代谢有2种途径：线粒体氧化磷酸化和糖酵解。正常哺乳动物细胞在有氧条件下，糖酵解被抑制。然而，1920年，德国生化学家Warburg发现：肝癌细胞的糖酵解活性较正常肝细胞活跃。提出：在氧气充足下，恶性肿瘤细胞糖酵解同样活跃，这种有氧糖酵解的代谢特征称为瓦博格效应，表现为葡萄糖摄取率高，糖酵解活跃，代谢产物乳酸含量高。 “瓦博格效应”疑问——“为什么肿瘤细胞大量消耗葡萄糖却不能高效产能？” * * However, both causes of the Warburg effect and its connection to biosynthesis are not well understood. Here we show that the tumour suppressor p53, the most frequently mutated gene in human tumours, inhibits the pentose phosphate pathway (PPP). 然而，瓦博格效应产生的原因以及它与癌细胞生物合成的关系，还不是十分清楚。在本文中，介绍了一种抑癌基因p53（在肿瘤细胞中发生变异频率较高的基因），p53可抑制戊糖磷酸途径（ pentose phosphate pathway ，PPP）。 * Through the PPP, p53 suppresses glucose consumption, NADPH production and biosynthesis. The p53 protein binds to glucose-6-phosphate dehydrogenase (G6PD), the first and rate-limiting enzyme of the PPP, and prevents the formation of the active dimer. 通过PPP，p53可抑制葡萄糖消耗、NADPH产生 及生物合成。p53可以与戊糖磷酸途径上的第一 步