Lysine succinylation (Ksucc) is an evolutionarily conserved and widespread post‐translational modification. Histone acetyltransferase 1 (HAT1) is a type B histone acetyltransferase, regulating the acetylation of both histone and non‐histone proteins. However, the role of HAT1 in succinylation modulation remains unclear. Here, we employ a quantitative proteomics approach to study succinylation in HepG2 cancer cells and find that HAT1 modulates lysine succinylation on various proteins including histones and non‐histones. HAT1 succinylates histone H3 on K122, contributing to epigenetic regulation and gene expression in cancer cells. Moreover, HAT1 catalyzes the succinylation of PGAM1 on K99, resulting in its increased enzymatic activity and the stimulation of glycolytic flux in cancer cells. Clinically, HAT1 is significantly elevated in liver cancer, pancreatic cancer, and cholangiocarcinoma tissues. Functionally, HAT1 succinyltransferase activity and the succinylation of PGAM1 by HAT1 play critical roles in promoting tumor progression in vitro and in vivo. Thus, we conclude that HAT1 is a succinyltransferase for histones and non‐histones in tumorigenesis.

中文翻译：

---

组蛋白乙酰转移酶 1 是一种用于组蛋白和非组蛋白的琥珀酰转移酶，可促进肿瘤发生

赖氨酸琥珀酰化（Ksucc）是一种进化上保守且广泛的翻译后修饰。组蛋白乙酰转移酶 1 (HAT1) 是一种 B 型组蛋白乙酰转移酶，可调节组蛋白和非组蛋白的乙酰化。然而，HAT1 在琥珀酰化调节中的作用仍不清楚。在这里，我们采用定量蛋白质组学方法研究 HepG2 癌细胞中的琥珀酰化，发现 HAT1 调节各种蛋白质（包括组蛋白和非组蛋白）的赖氨酸琥珀酰化。HAT1 琥珀酰化 K122 上的组蛋白 H3，有助于癌细胞的表观遗传调控和基因表达。此外，HAT1 催化 PGAM1 在 K99 上的琥珀酰化，导致其酶活性增加并刺激癌细胞中的糖酵解通量。临床上，HAT1 在肝癌中显着升高，胰腺癌和胆管癌组织。在功能上，HAT1 琥珀酰转移酶活性和 HAT1 对 PGAM1 的琥珀酰化在促进肿瘤进展中起关键作用体外和体内。因此，我们得出结论，HAT1 是肿瘤发生中组蛋白和非组蛋白的琥珀酰转移酶。