Acetylation site specificities of lysine deacetylase inhibitors in human cells

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Acetylation site specificities of lysine deacetylase inhibitors in human cells. / Schölz, Christian; Weinert, Brian Tate; Wagner, Sebastian A; Beli, Petra; Miyake, Yasuyuki; Qi, Jun; Jensen, Lars J; Streicher, Werner; McCarthy, Anna R; Westwood, Nicholas J; Lain, Sonia; Cox, Jürgen; Matthias, Patrick; Mann, Matthias; Bradner, James E; Choudhary, Chuna Ram.

In: Nature Biotechnology, Vol. 33, 2015, p. 415–423.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Schölz, C, Weinert, BT, Wagner, SA, Beli, P, Miyake, Y, Qi, J, Jensen, LJ, Streicher, W, McCarthy, AR, Westwood, NJ, Lain, S, Cox, J, Matthias, P, Mann, M, Bradner, JE & Choudhary, CR 2015, 'Acetylation site specificities of lysine deacetylase inhibitors in human cells', Nature Biotechnology, vol. 33, pp. 415–423. https://doi.org/10.1038/nbt.3130

APA

Schölz, C., Weinert, B. T., Wagner, S. A., Beli, P., Miyake, Y., Qi, J., Jensen, L. J., Streicher, W., McCarthy, A. R., Westwood, N. J., Lain, S., Cox, J., Matthias, P., Mann, M., Bradner, J. E., & Choudhary, C. R. (2015). Acetylation site specificities of lysine deacetylase inhibitors in human cells. Nature Biotechnology, 33, 415–423. https://doi.org/10.1038/nbt.3130

Vancouver

Schölz C, Weinert BT, Wagner SA, Beli P, Miyake Y, Qi J et al. Acetylation site specificities of lysine deacetylase inhibitors in human cells. Nature Biotechnology. 2015;33:415–423. https://doi.org/10.1038/nbt.3130

Author

Schölz, Christian ; Weinert, Brian Tate ; Wagner, Sebastian A ; Beli, Petra ; Miyake, Yasuyuki ; Qi, Jun ; Jensen, Lars J ; Streicher, Werner ; McCarthy, Anna R ; Westwood, Nicholas J ; Lain, Sonia ; Cox, Jürgen ; Matthias, Patrick ; Mann, Matthias ; Bradner, James E ; Choudhary, Chuna Ram. / Acetylation site specificities of lysine deacetylase inhibitors in human cells. In: Nature Biotechnology. 2015 ; Vol. 33. pp. 415–423.

Bibtex

@article{a700550bd0104290ad1530dd1d703344,
title = "Acetylation site specificities of lysine deacetylase inhibitors in human cells",
abstract = "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.",
author = "Christian Sch{\"o}lz and Weinert, {Brian Tate} and Wagner, {Sebastian A} and Petra Beli and Yasuyuki Miyake and Jun Qi and Jensen, {Lars J} and Werner Streicher and McCarthy, {Anna R} and Westwood, {Nicholas J} and Sonia Lain and J{\"u}rgen Cox and Patrick Matthias and Matthias Mann and Bradner, {James E} and Choudhary, {Chuna Ram}",
year = "2015",
doi = "10.1038/nbt.3130",
language = "English",
volume = "33",
pages = "415–423",
journal = "Nature Biotechnology",
issn = "1087-0156",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - Acetylation site specificities of lysine deacetylase inhibitors in human cells

AU - Schölz, Christian

AU - Weinert, Brian Tate

AU - Wagner, Sebastian A

AU - Beli, Petra

AU - Miyake, Yasuyuki

AU - Qi, Jun

AU - Jensen, Lars J

AU - Streicher, Werner

AU - McCarthy, Anna R

AU - Westwood, Nicholas J

AU - Lain, Sonia

AU - Cox, Jürgen

AU - Matthias, Patrick

AU - Mann, Matthias

AU - Bradner, James E

AU - Choudhary, Chuna Ram

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

U2 - 10.1038/nbt.3130

DO - 10.1038/nbt.3130

M3 - Journal article

C2 - 25751058

VL - 33

SP - 415

EP - 423

JO - Nature Biotechnology

JF - Nature Biotechnology

SN - 1087-0156

ER -

ID: 135114940