PXD015825-1

PXD015825 is an original dataset announced via ProteomeXchange.

Title	Discovery of a potent and selective covalent inhibitor and activity-based probe for UCHL1, with anti-fibrotic activity
Description	Ubiquitin carboxy-terminal hydrolase L1 (UCHL1) is a deubiquitinating enzyme (DUB) that is very highly expressed in human brain. UCHL1 has been proposed as a potential therapeutic target in neurodegeneration, cancer, and liver and lung fibrosis, however bona fide molecular functions of UCHL1 are yet to be elucidated. Herein we characterize a potent and selective inhibitor and activity-based probe (IMP-1710) for UCHL1 based on a covalent inhibitor scaffold, and its application to identify and quantify target proteins in intact human cells. IMP-1710 stereoselectively labels the catalytic cysteine of UCHL1 at low nanomolar concentration, and we show that a previously claimed UCHL1 inhibitor (LDN-57444) fails to engage UCHL1 in cells. We further demonstrate that potent UCHL1 inhibitors selectively block pro-fibrotic responses in a cellular model of idiopathic pulmonary fibrosis (IPF), supporting a potential therapeutic role for UCHL1 inhibition.
HostingRepository	PRIDE
AnnounceDate	2020-11-13
AnnouncementXML	Submission_2020-11-13_04:17:38.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Nattawadee Panyain
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-10-15 01:21:51	ID requested
⏵ 1	2020-11-13 04:17:38	announced
2	2024-10-22 05:15:02	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: Activity Based-Probe Profiling, Human, Deubiquitination, UCHL1, Chemical Proteomics

Edward W. Tate
contact affiliation	Department of Chemistry, Molecular Sciences Research Hub, Imperial College London, London, W12 0BZ, UK
contact email	e.tate@imperial.ac.uk
lab head
Nattawadee Panyain
contact affiliation	Imperial College London
contact email	nattawadee.panyain14@imperial.ac.uk
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/2020/11/PXD015825

PRIDE project URI

• PRIDE
  1. PXD015825
     1. Label: PRIDE project
     2. Name: Discovery of a potent and selective covalent inhibitor and activity-based probe for UCHL1, with anti-fibrotic activity