کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2108092 | 1083721 | 2013 | 13 صفحه PDF | دانلود رایگان |

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
Journal: - Volume 23, Issue 4, 15 April 2013, Pages 464–476