SAHA Regulates Histone Acetylation, Butyrylation, and Protein Expression in Neuroblastoma

Emerging evidence suggests that suberoylanilide hydroxamic acid (SAHA), a clinically approved HDAC inhibitor for cutaneous T-cell lymphoma, shows promising clinical benefits in neuroblastoma, the most common extra cranial solid neoplasm with limited choice of therapeutic intervention. However, the molecular mechanism under which the compound exerts its antitumor effect remains elusive. Here we report a quantitative proteomics study that determines changes of protein expression, histone lysine acetylation, and butyrylation in response to SAHA treatment. We detected and quantified 28 histone lysine acetylation and 18 histone lysine butyrylation marks, most of which are dramatically induced by SAHA. Importantly, we identified 11 histone K_bu sites as novel histone marks in human cells. Furthermore, quantitative proteomic analysis identified 5426 proteins, among which 510 proteins were up-regulated and 508 proteins were down-regulated (significant <i>p</i> value