Deacetylation by SIRT1 promotes the tumor-suppressive activity of HINT1 by enhancing its binding capacity for β-catenin or MITF in colon cancer and melanoma cells

Abstract

Experimental & molecular medicine: tumor suppression: minor modifications aid cancer control A crucial modification to the tumor-suppressing gene HINT1 helps slow the spread of colon cancer and melanoma according to researchers in South Korea. HINT1 is known to bind to and inhibit several tumor-promoting transcription factors, but it is unclear how this process is regulated. Hyun-Seok Kim at Ewha Womans University in Seoul and co-workers focused on SIRT1, an enzyme that deacetylates, i.e., removes acetyl groups from, various important proteins. They found that the deacetylation of HINT1 by SIRT1 promotes the capacity of HINT1 to bind to transcription factors, thereby enhancing its tumor-suppressing function. Mutant colon cancer and melanoma cell lines with completely deacetylated HINT1 showed significantly reduced growth. The researchers suggest that acetylation and other reversible modifications of HINT1, such as phosphorylation, could be useful in clinical treatments.