A directed mutation of a putative nuclear localization signal (NLS) in Acss2 residing in the carboxy terminal portion that changes two basic (RK) to two acidic (ED) amino acid residues abrogates HIF-2 acetylation, blunts HIF-2 dependent signaling, and impairs flank tumor growth in cancer cells expressing mutant Acss2 (7). Here, ACSS2 is linked to cancer.