Acetylation site specificities of lysine deacetylase inhibitors in human cells

Christian Schölz, Brian T. Weinert, Sebastian A. Wagner, Petra Beli, Yasuyuki Miyake, Yun Qi, Lars J. Jensen, Werner Streicher, Anna Rose McCarthy, Nicholas James Westwood, Sonya Lain, Jürgen Cox, Patrick Matthias, Matthias Mann, James E. Bradner, Chunaram Choudhary

Research output: Contribution to journalArticlepeer-review

164 Citations (Scopus)


Lysine deacetylases inhibitors (KDACIs) are used in basic research, and many are being investigated in clinical trials for treatment of cancer and other diseases. However, their specificities in cells are incompletely characterized. Here we used quantitative mass spectrometry (MS) to obtain acetylation signatures for 19 different KDACIs, covering all 18 human lysine deacetylases. Most KDACIs increased acetylation of a small, specific subset of the acetylome, including sites on histones and other chromatin-associated proteins. Inhibitor treatment combined with genetic deletion showed that the effects of the pan-sirtuin inhibitor nicotinamide are primarily mediated by SIRT1 inhibition. Furthermore, we confirmed that the effects of tubacin and bufexamac on cytoplasmic proteins result from inhibition of HDAC6. Bufexamac also triggered an HDAC6-independent, hypoxia-like response by stabilizing HIF1-α, providing a possible mechanistic explanation of its adverse, pro-inflammatory effects. Our results offer a systems view of KDACI specificities, providing a framework for studying function of acetylation and deacetylases.
Original languageEnglish
JournalNature Biotechnology
Early online date9 Mar 2015
Publication statusPublished - 2015


  • Acetylation
  • Deacetylase inhibitor
  • HDAC
  • KDAC
  • Mass spectrometry
  • Proteomics
  • Sirtuin
  • Nicotinamide
  • Tenovin-6
  • Bufexamac


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