• Home
  • Search Results
  • Acetylation stabilizes ATP-citrate lyase to promote lipid biosynthesis and tumor growth.

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

Molecular cell (2013-08-13)
Ruiting Lin, Ren Tao, Xue Gao, Tingting Li, Xin Zhou, Kun-Liang Guan, Yue Xiong, Qun-Ying Lei
ABSTRACT

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 P300/calcium-binding protein (CBP)-associated factor (PCAF) acetyltransferase under high glucose and increases ACLY stability by blocking its ubiquitylation and degradation. Conversely, the protein deacetylase sirtuin 2 (SIRT2) deacetylates and destabilizes ACLY. Substitution of 3K abolishes ACLY ubiquitylation and promotes de novo lipid synthesis, cell proliferation, and tumor growth. Importantly, 3K acetylation of ACLY is increased in human lung cancers. Our study reveals a crosstalk between acetylation and ubiquitylation by competing for the same lysine residues in the regulation of fatty acid synthesis and cell growth in response to glucose.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-phospho-ATP-Citrate Lyase (pSer454) antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-ACLY antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution, Ab1
Sigma-Aldrich
Anti-ACLY antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
Sigma-Aldrich
Anti-ACLY antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution