Abstract
IMP dehydrogenase 2 (IMPDH2) occupies a crucial position in purine biosynthesis and GTP level control. Although IMPDH2 are shown to be related to cancer or neurodevelopmental disease, post-translation modifications (PTMs) of IMPDH2 and their roles in disease are understudied. We report that acetylation on K208 residue disrupts octamer formation and makes the protein more resistant to GTP inhibition, while acetylation on K438 residue impairs the enzyme activity. We also identify ⍺-tubulin acetyltransferase 1 (ATAT1) as an acetyltransferase of IMPDH2, and histone deacetylase 6 (HDAC6) as a deacetylase of IMPDH2 K208Ac. These findings illustrate the importance of IMPDH2 acetylation in GTP pool regulation, and identify a mechanism that connects GTP metabolism to cell migration.