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Lysine-5 Acetylation Negatively Regulates Lactate Dehydrogenase A and Is Decreased in Pancreatic Cancer

2013; Cell Press; Volume: 23; Issue: 4 Linguagem: Inglês

10.1016/j.ccr.2013.02.005

1878-3686

Di Zhao, Shao-Wu Zou, Ying Liu, Xin Zhou, Yan Mo, Ping Wang, Yan-hui Xu, Bo Dong, Yue Xiong, Qun‐Ying Lei, Kun‐Liang Guan,

Histone Deacetylase Inhibitors Research

Tumor cells commonly have increased glucose uptake and lactate accumulation. Lactate is produced from pyruvate by lactate dehydrogenase A (LDH-A), which is frequently overexpressed in tumor cells and is important for cell growth. Elevated transcription by c-Myc or HIF1α may contribute to increased LDH-A in some cancer types. Here, we show that LDH-A is acetylated at lysine 5 (K5) and that this acetylation inhibits LDH-A activity. Furthermore, the K5-acetylated LDH-A is recognized by the HSC70 chaperone and delivered to lysosomes for degradation. Replacement of endogenous LDH-A with an acetylation mimetic mutant decreases cell proliferation and migration. Importantly, K5 acetylation of LDH-A is reduced in human pancreatic cancers. Our study reveals a mechanism of LDH-A upregulation in pancreatic cancers.