Selective inhibitors of SIRT2 regulate perinuclear α-tubulin acetylation, migration, and invasion of breast cancer cells
Nielsen, A. L.; Rajabi, N.; Kudo, N.; Larsen, K. L.; Fontenas, M.; Lucidi, A.; Madsen, A. S.; Yoshida, M.; Olsen, C. A.
Show abstract
Sirtuin 2 (SIRT2) is a protein deacylase enzyme that removes acetyl groups and longer chain acyl groups from post-translationally modified lysine residues. It affects diverse biological functions in the cell and has been considered a drug target in relation to both neurodegenerative diseases and cancer. Therefore, access to well-characterized and robust tool compounds is essential for the continued investigation of the complex functions of this enzyme. Here, we report a collection of probes that are potent, selective, stable in serum, water-soluble, amenable to cell culture experiments, and inhibit both SIRT2 deacetylation and demyristoylation. Compared to the current landscape of SIRT2 inhibitors, this is a unique ensemble of features built into a single compound. We expect the developed chemotypes to find broad application in the interrogation of SIRT2 functions in both healthy and diseased cells, and to provide a foundation for the development of future therapeutics.
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