PXD001377

PXD001377 is an original dataset announced via ProteomeXchange.

Title	Unraveling Lysine Deacetylase Inhibitor Specificities for Endogenous Acetylation Sites
Description	Lysine 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.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_03:58:27.505.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christian Schölz
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2014-10-03 01:58:32	ID requested
1	2015-02-16 09:37:02	announced
2	2017-03-29 00:19:23	announced	Updated publication reference for PubMed record(s): 25751058.
⏵ 3	2024-10-22 03:58:35	announced	2024-10-22: Updated project metadata.

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]

10.1038/nbt.3130;

ProteomeXchange project tag: PRIME-XS Project

curator keyword: Biomedical

submitter keyword: proteomics, bufexamac, mass spectrometry, SILAC, nicotinamide, HDAC,Acetylation, tenovin-6, KDAC, sirtuin, deacetylase inhibitor

Chunaram Choudhary
contact affiliation	The Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, Dept. of Proteomics and Cell Signaling
contact email	chuna.choudhary@cpr.ku.dk
lab head
Christian Schölz
contact affiliation	Novo Nordisk Foundation Center for Protein Research; University of Copenhagen
contact email	christian.scholz@cpr.ku.dk
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2015/02/PXD001377

PRIDE project URI

• PRIDE
  1. PXD001377
     1. Label: PRIDE project
     2. Name: Unraveling Lysine Deacetylase Inhibitor Specificities for Endogenous Acetylation Sites