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Acetyl-coenzyme A synthetase 2 (ACSS2) is a nuclear and cytoplasmic enzyme that catalyzes the conversion of acetate and coenzyme A to acetyl-CoA, using ATP as a cofactor[1][2][8]. Acetyl-CoA produced by ACSS2 supports key biosynthetic and regulatory pathways, including lipid synthesis and histone acetylation, which impact gene expression and cellular differentiation[1][2][8]. ACSS2 is critically involved in cellular adaptation to nutrient and oxygen stress, enabling cancer cells to survive in challenging tumor microenvironments by reprogramming metabolism for the production of acetyl-CoA from available acetate[1][6][7]. Downregulation or inhibition of ACSS2 impairs histone acetylation, energy metabolism, and can reduce tumor cell viability; hence, ACSS2 is regarded as a promising therapeutic target in cancer and potentially in metabolic or neurodegenerative disease treatment[1][2][7][8].
Inhibition of ACSS2 can restrict the supply of acetyl-CoA, limiting tumor cell growth and survival Modulation of histone acetylation and gene expression by affecting acetyl-CoA availability
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