Article ID Journal Published Year Pages File Type
2108092 Cancer Cell 2013 13 Pages PDF
Abstract

SummaryTumor 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.

► Acetylation inhibits LDH-A activity ► Acetylation targets LDH-A for chaperone-mediated autophagy ► SIRT2 regulates LDH-A acetylation ► Pancreatic cancer has decreased acetylation and increased protein levels of LDH-A

Related Topics
Life Sciences Biochemistry, Genetics and Molecular Biology Cancer Research
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