کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2108092 1083721 2013 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Lysine-5 Acetylation Negatively Regulates Lactate Dehydrogenase A and Is Decreased in Pancreatic Cancer
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Lysine-5 Acetylation Negatively Regulates Lactate Dehydrogenase A and Is Decreased in Pancreatic Cancer
چکیده انگلیسی

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

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 23, Issue 4, 15 April 2013, Pages 464–476
نویسندگان
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