PXD023583

PXD023583 is an original dataset announced via ProteomeXchange.

Title	Chemo-proteomics exploration of HDAC degradability by small molecule degraders
Description	Targeted protein degradation refers to the use of small molecule protein-protein dimerizers that recruit a ubiquitin E3 ligase to a protein of interest for chemically induced degradation. Here we combine systematic exploration of 51 degraders designed to broadly target the HDAC family of proteins with chemo-proteomics, to map the degradability of zinc-dependent HDAC proteins. Our dataset provides chemical leads for targeting HDACs 1-8 and 10, and investigates important aspects of degrader design such as recruited ligase and linker length and position, to assist chemical design prioritization. We discover that targeting HDACs often results in collateral degradation of the multi-protein complexes that HDACs belong to, offering a new mechanism of controlling chromatin structure. This database is an open source resource for facilitating accelerated degrader design and development for this epigenetic class of enzymes.
HostingRepository	PRIDE
AnnounceDate	2021-07-30
AnnouncementXML	Submission_2021-07-29_21:58:33.182.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Eric Fischer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-01-14 01:49:20	ID requested
1	2021-07-29 17:33:58	announced
⏵ 2	2021-07-29 21:58:33	announced	2021-07-30: Updated project metadata.

10.1016/J.CHEMBIOL.2021.07.002;

Xiong Y, Donovan KA, Eleuteri NA, Kirmani N, Yue H, Razov A, Krupnick NM, Nowak RP, Fischer ES, Chemo-proteomics exploration of HDAC degradability by small molecule degraders. Cell Chem Biol, 28(10):1514-1527.e4(2021) [pubmed]

submitter keyword: PROTAC, IMiD, degrader, ubiquitin, targeted degradation, E3 ligase,HDAC

Eric Fischer
contact affiliation	Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA., Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
contact email	eric_fischer@dfci.harvard.edu
lab head
Eric Fischer
contact affiliation	Dana-Farber Cancer Institute
contact email	eric_fischer@dfci.harvard.edu
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/2021/07/PXD023583

PRIDE project URI

• PRIDE
  1. PXD023583
     1. Label: PRIDE project
     2. Name: Chemo-proteomics exploration of HDAC degradability by small molecule degraders