当前位置：
X-MOL 学术
›
Nat. Commun.
›
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.)
O-GlcNAcylation of PGK1 coordinates glycolysis and TCA cycle to promote tumor growth.
Nature Communications ( IF 14.7 ) Pub Date : 2020-01-07 , DOI: 10.1038/s41467-019-13601-8 Hao Nie 1 , Haixing Ju 2 , Jiayi Fan 1 , Xiaoliu Shi 1 , Yaxian Cheng 1 , Xiaohui Cang 3 , Zhiguo Zheng 2 , Xiaotao Duan 4 , Wen Yi 1
Nature Communications ( IF 14.7 ) Pub Date : 2020-01-07 , DOI: 10.1038/s41467-019-13601-8 Hao Nie 1 , Haixing Ju 2 , Jiayi Fan 1 , Xiaoliu Shi 1 , Yaxian Cheng 1 , Xiaohui Cang 3 , Zhiguo Zheng 2 , Xiaotao Duan 4 , Wen Yi 1
Affiliation
|
Many cancer cells display enhanced glycolysis and suppressed mitochondrial metabolism. This phenomenon, known as the Warburg effect, is critical for tumor development. However, how cancer cells coordinate glucose metabolism through glycolysis and the mitochondrial tricarboxylic acid (TCA) cycle is largely unknown. We demonstrate here that phosphoglycerate kinase 1 (PGK1), the first ATP-producing enzyme in glycolysis, is reversibly and dynamically modified with O-linked N-acetylglucosamine (O-GlcNAc) at threonine 255 (T255). O-GlcNAcylation activates PGK1 activity to enhance lactate production, and simultaneously induces PGK1 translocation into mitochondria. Inside mitochondria, PGK1 acts as a kinase to inhibit pyruvate dehydrogenase (PDH) complex to reduce oxidative phosphorylation. Blocking T255 O-GlcNAcylation of PGK1 decreases colon cancer cell proliferation, suppresses glycolysis, enhances the TCA cycle, and inhibits tumor growth in xenograft models. Furthermore, PGK1 O-GlcNAcylation levels are elevated in human colon cancers. This study highlights O-GlcNAcylation as an important signal for coordinating glycolysis and the TCA cycle to promote tumorigenesis.
中文翻译：
PGK1的O-GlcNAcylation协调糖酵解和TCA循环以促进肿瘤生长。
许多癌细胞显示出增强的糖酵解和抑制的线粒体代谢。这种现象被称为Warburg效应，对肿瘤发展至关重要。但是，癌细胞如何通过糖酵解和线粒体三羧酸（TCA）循环来协调葡萄糖代谢尚不清楚。我们在这里证明，磷酸甘油酸激酶1（PGK1），在糖酵解中的第一个ATP产生酶，在苏氨酸255（T255）上可逆和动态地被O-连接的N-乙酰氨基葡萄糖（O-GlcNAc）修饰。O-GlcNAcylation激活PGK1活性以增强乳酸的产生，并同时诱导PGK1易位到线粒体中。在线粒体内，PGK1充当激酶来抑制丙酮酸脱氢酶（PDH）复合物，从而减少氧化磷酸化。在异种移植模型中，PGK1的T255 O-GlcNAcy阻断可降低结肠癌细胞的增殖，抑制糖酵解，增强TCA循环并抑制肿瘤的生长。此外，PGK10 O-GlcNAcylation水平在人类结肠癌中升高。这项研究强调了O-GlcNAcylation是协调糖酵解和TCA循环促进肿瘤发生的重要信号。
更新日期：2020-01-07
中文翻译：
PGK1的O-GlcNAcylation协调糖酵解和TCA循环以促进肿瘤生长。
许多癌细胞显示出增强的糖酵解和抑制的线粒体代谢。这种现象被称为Warburg效应，对肿瘤发展至关重要。但是，癌细胞如何通过糖酵解和线粒体三羧酸（TCA）循环来协调葡萄糖代谢尚不清楚。我们在这里证明，磷酸甘油酸激酶1（PGK1），在糖酵解中的第一个ATP产生酶，在苏氨酸255（T255）上可逆和动态地被O-连接的N-乙酰氨基葡萄糖（O-GlcNAc）修饰。O-GlcNAcylation激活PGK1活性以增强乳酸的产生，并同时诱导PGK1易位到线粒体中。在线粒体内，PGK1充当激酶来抑制丙酮酸脱氢酶（PDH）复合物，从而减少氧化磷酸化。在异种移植模型中，PGK1的T255 O-GlcNAcy阻断可降低结肠癌细胞的增殖，抑制糖酵解，增强TCA循环并抑制肿瘤的生长。此外，PGK10 O-GlcNAcylation水平在人类结肠癌中升高。这项研究强调了O-GlcNAcylation是协调糖酵解和TCA循环促进肿瘤发生的重要信号。
京公网安备 11010802027423号