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PXD001377

PXD001377 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleUnraveling Lysine Deacetylase Inhibitor Specificities for Endogenous Acetylation Sites
DescriptionLysine deacetylases (KDACs) are important regulators of biological processes. KDAC inhibitors (KDACIs) are important tools for basic research and attractive therapeutic candidates, yet their effects on in-vivo acetylation sites are poorly known. Here we obtained acetylation signatures for 19 different KDACIs that cover all known deacetylases. Most KDACIs targeting non-sirtuin deacetylases increased acetylation of a small, but specific, subset of the acetylome, and included sites on histone and other chromatin-associated proteins. Using a combination of genetic deletion and inhibitor treatment we found that the sirtuin inhibitor nicotinamide increased acetylation via SIRT1 inhibition, whereas tubacin and bufexamac affected cytoplasmic proteins through inhibition of HDAC6. Bufexamac additionally triggered an HDAC6-independent hypoxia-like response by stabilizing HIF1-α, providing a potential mechanistic basis for its adverse pro-inflammatory effects. Our results provide a systematic view of the scope and specificities of KDACIs for acetylation sites, and uncovered unexpected acetylation profiles for several of commonly used inhibitors.
HostingRepositoryPRIDE
AnnounceDate2017-03-29
AnnouncementXMLSubmission_2017-03-29_00:19:18.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterChristian Schölz
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListacetylated residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02014-10-03 01:58:32ID requested
12015-02-16 09:37:02announced
22017-03-29 00:19:23announcedUpdated publication reference for PubMed record(s): 25751058.
Publication List
Sch, ö, lz 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 C, Acetylation site specificities of lysine deacetylase inhibitors in human cells. Nat Biotechnol, 33(4):415-23(2015) [pubmed]
Keyword List
ProteomeXchange project tag: PRIME-XS Project
curator keyword: Biomedical
submitter keyword: Acetylation, deacetylase inhibitor, SILAC, HDAC, KDAC, mass spectrometry, proteomics, sirtuin, nicotinamide, tenovin-6, bufexamac
Contact List
Chunaram Choudhary
contact affiliationThe Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, Dept. of Proteomics and Cell Signaling
contact emailchuna.choudhary@cpr.ku.dk
lab head
Christian Schölz
contact affiliationNovo Nordisk Foundation Center for Protein Research; University of Copenhagen
contact emailchristian.scholz@cpr.ku.dk
dataset submitter
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