乙酰化
赖氨酸
磷酸戊糖途径
组蛋白
生物化学
酶
磷酸化
脱氢酶
泛素
生物
化学
细胞生物学
糖酵解
氨基酸
DNA
基因
作者
Fang Wu,Natali H. Muskat,Inbar Dvilansky,Omri Koren,Amit Shahar,Roi Gazit,Natalie Elia,Eyal Arbely
标识
DOI:10.1038/s41467-023-41895-2
摘要
Abstract Lysine acetylation has been discovered in thousands of non-histone human proteins, including most metabolic enzymes. Deciphering the functions of acetylation is key to understanding how metabolic cues mediate metabolic enzyme regulation and cellular signaling. Glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme in the pentose phosphate pathway, is acetylated on multiple lysine residues. Using site-specifically acetylated G6PD, we show that acetylation can activate (AcK89) and inhibit (AcK403) G6PD. Acetylation-dependent inactivation is explained by structural studies showing distortion of the dimeric structure and active site of G6PD. We provide evidence for acetylation-dependent K95/97 ubiquitylation of G6PD and Y503 phosphorylation, as well as interaction with p53 and induction of early apoptotic events. Notably, we found that the acetylation of a single lysine residue coordinates diverse acetylation-dependent processes. Our data provide an example of the complex roles of acetylation as a posttranslational modification that orchestrates the regulation of enzymatic activity, posttranslational modifications, and apoptotic signaling.
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