Lysine-5 Acetylation Negatively Regulates Lactate Dehydrogenase A and Is Decreased in Pancreatic Cancer (Cancer Cell, 2013, 23:464-76)

報告日期: 2014/04/25
報告時間: 3:10/4:00
報告學生: 洪妤萱(以英文報告)
講評老師: 蔡少正
附件下載: 下載[1399-1396958529-1.pdf] 

Lysine-5 acetylation negatively regulates lactate dehydrogenase A        and is decreased in pancreatic cancer
Cancer Cell. 2013;23:464-76

Speaker: Hung, Yu-Hsuan                        Date: 2014/4/25 15:10-16:00

Commentator: Pro. Tsai, Shaw-Jeng                          Place: Room 602

Glycolysis is one of the important characteristics in cancer cells and overexpression of glycolytic enzymes at mRNA and subsequent protein levels are frequently observed during tumorigenesis. In addition, cancer cells also apply other strategies, such as post-translational modification (PTM), to regulate the expression of oncogenes and tumor suppressor genes. In their previous study, the authors of the present study identified that many metabolic enzymes, including those of glycolysis, can be acetylated (1) and this may affect their protein expression and function (2). In this study, they aimed to investigate the importance of acetylation on function and protein expression of glycolytic enzymes in terms of lactate dehydrogenase-A (LDH-A). In the first part, the authors investigated the possibility and impact of acetylation on the function of LDH-A. They found out that deacetylase inhibitor treatment increases the acetylation status of LDH-A, and mass spectrometry analysis revealed that lysine 5 is an important residue to be acetylated on LDH-A and is conserved across multiple species. Furthermore, lysine 5 (K5)-acetylated LDH-A displays decreased enzymatic activity and this can be negatively regulated by its upstream regulator SIRT2 deacetylase. In the second part, the authors further ask the impact of K5-acetylation on LDH-A protein expression, and identified that K5-acetylated LDH-A displayed decreased protein expression which is not associated with proteasomal degradation but is depended on autophagy, among which the selective chaperone-mediated autophagy, instead of non-selective macro-autophagy, is responsible for degradation of K5-acetylated LDH-A. In the last part, the authors investigated the importance of K5-acetylated LDH-A during tumorigenesis in terms of pancreatic cancer and confirmed the results in human clinical specimens. They identified that the acetylation mimetic of LDH-A displayed decreased cell proliferation and migration ability in pancreatic cancer cell in vitro and in vivo, which is associated with decrease in lactate production. Above phenomenon can be further confirmed in human clinical specimens, as the increase in LDH-A and SIRT2 expression as well as decrease in K5-acetylated LDH-A are different with statistical significance in tumor tissues when compared to those of normal tissues. In conclusion, this study pointed out the importance of acetylation in regulating the expression and function of a glycolytic enzyme LDH-A, which may shed new light on the mechanisms in cancer metabolism.


1. Zhao S, et al. Regulation of cellular metabolism by protein lysine acetylation. Science. 2010;327:1000-4

2. Guan KL, Xiong Y. Regulation of intermediary metabolism by protein acetylation. Trends Biochem Sci. 2011;36:108-16