Acetylation Antagonizes Ubiquitylation To Stabilize ATP-citrate Lyase And Promote Lipid Biosynthesis And Tumor Growth

Protein lysine acetylation has emerged as a key posttranslational modification in celluar regulation in recent years. Many studies have shown that besides histone and nuclear proteins, lysine acetylation also plays as a widespread extra nuclear modification in cellular regulation. Many cytoplasmic proteins is potentially acetylated. Notably, nearly all metabolism enzymes were identified to be acetylated. Uncontrolled cellular metabolism is a hallmark of cancer. We study on the key enzymes of tumor cell metabolism, we could shed light on thefunction role of lysine acetylation on tumor cell proliferation. Our work would provide not only the oncology theory supportively but also the potentially therapy target in future.Our work focuses on the acetylation regulation of ACLY and its function role in cancer cell growth. Firstly, We reported acetylation at K540, K546, and K554of ACLY protects it from ubiquitin-mediated protein degradation, in response to cellular glucose condition. Secondly, ACLY is acetylated by PCAF acetyltransferase to enhance its protein stability. In contrast, SIRT2can deacetylate and destabilize ACLY. Thirdly, we reported the acetylation of ACLY can promote cell proliferation and lipid uptake in human NSCLC A549cells. Furthermore, Xenograft experiments showed ACLY acetylation facilitate tumor growth in vivo. Moreover, the acetylation of ACLY was increased in human lung carcinoma clinical samples, demonstrated the correlation between lysine acetylation and tumorigenesis.