The present data reveal that CBP- and SIRT1-driven reversible acetylation of HINT1 at both K21 and K30 affects the capacity of HINT1 to bind to β-catenin or MITF, which, in turn, can influence its tumor-suppressive activity in cancer cell lines and in an in vivo xenograft mouse model. The gene discussed is HINT1; the disease is neoplasm.