ATP citrate lyase inhibition can suppress tumor cell growth

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ACLY (ATP citrate lyase)

Other names: ACL, ATPCL, CLATP HGNC (Hugo): ACLY Location: 17q21.2 Note Note that the International Union for Biochemistry and Molecular Biology (IUBMB)'s enzyme nomenclature accepts ATP citrate synthase as the name for ACLY's encoded protein (EC 2.3.3.8). However, ATP citrate lyase is more commonly used and other names include citrate cleavage enzyme, ATP-citrate (pro-S)-lyase, ATPCL, CLATP. A...

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Acetylation stabilizes ATP-citrate lyase to promote lipid biosynthesis and tumor growth.

Increased fatty acid synthesis is required to meet the demand for membrane expansion of rapidly growing cells. ATP-citrate lyase (ACLY) is upregulated or activated in several types of cancer, and inhibition of ACLY arrests proliferation of cancer cells. Here we show that ACLY is acetylated at lysine residues 540, 546, and 554 (3K). Acetylation at these three lysine residues is stimulated by P30...

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ATP-citrate lyase deficiency in the mouse.

ATP-citrate lyase (Acly) is one of two cytosolic enzymes that synthesize acetyl-coenzyme A (CoA). Because acetyl-CoA is an essential building block for cholesterol and triglycerides, Acly has been considered a therapeutic target for hyperlipidemias and obesity. To define the phenotype of Acly-deficient mice, we created Acly knockout mice in which a beta-galactosidase marker is expressed from Ac...

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ATP citrate lyase knockdown induces growth arrest and apoptosis through different cell- and environment-dependent mechanisms.

ATP citrate lyase (ACLY) is a cytosolic enzyme that catalyzes generation of acetyl-CoA, which is a vital building block for fatty acid, cholesterol, and isoprenoid biosynthesis. ACLY is upregulated in several types of cancer, and its inhibition induces proliferation arrest in certain cancer cells. As ACLY is involved in several pathways, its downregulation may affect multiple processes. Here, w...

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Liver-specific ATP-citrate lyase inhibition by bempedoic acid decreases LDL-C and attenuates atherosclerosis

Despite widespread use of statins to reduce low-density lipoprotein cholesterol (LDL-C) and associated atherosclerotic cardiovascular risk, many patients do not achieve sufficient LDL-C lowering due to muscle-related side effects, indicating novel treatment strategies are required. Bempedoic acid (ETC-1002) is a small molecule intended to lower LDL-C in hypercholesterolemic patients, and has be...

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ژورنال

عنوان ژورنال: Cancer Cell

سال: 2005

ISSN: 1535-6108

DOI: 10.1016/j.ccr.2005.09.008