PXD041346-1

PXD041346 is an original dataset announced via ProteomeXchange.

Title	Cellular Validation of Chemically Improved Inhibitor Identifies Monoubiquitination on OTUB2
Description	Ubiquitin thioesterase OTUB2, a cysteine protease from the ovarian tumor (OTU) deubiquitinase superfamily, is associated with enhanced expression during tumor progression and metastasis. Development of OTUB2 inhibitors is therefore believed to be therapeutically important, yet potent and selective small-molecule inhibitors targeting OTUB2 are scarce. Here, we describe the development of an improved OTUB2 inhibitor, LN5P45, comprising a chloroacethydrazide moiety that covalently reacts to the active-site cysteine residue. When added to cells, LN5P45 shows outstanding target engagement and proteome-wide selectivity. Importantly, we found that LN5P45 and the other OTUB2 inhibitors strongly induce monoubiquitination of OTUB2 via lysine 31. Thus, our findings provide novel insights for the design of future OTUB2-related therapeutics and open new questions regarding the understanding of OTUB2 regulation at the post-translational modification level.
HostingRepository	PRIDE
AnnounceDate	2023-06-27
AnnouncementXML	Submission_2023-06-27_03:49:49.631.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	RaymanTjokrodirijo
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	ubiquitinylated lysine
Instrument	Orbitrap Fusion Lumos; Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-04-05 03:52:30	ID requested
⏵ 1	2023-06-27 03:49:50	announced

Dataset with its publication pending

submitter keyword: OTUB2, small-molecule inhibitor, monoubiquitination

Peter A. vanVeelen
contact affiliation	Head Proteomics Group Leiden University Medical Center, Center for Proteomics and Metabolomics, PO Box 9600, Postal zone P1-Q, 2300 RC Leiden, The Netherlands
contact email	P.A.van_Veelen@lumc.nl
lab head
RaymanTjokrodirijo
contact affiliation	Leiden University Medical Center, Proteomics group
contact email	R.T.N.Tjokrodirijo@lumc.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD041346
     1. Label: PRIDE project
     2. Name: Cellular Validation of Chemically Improved Inhibitor Identifies Monoubiquitination on OTUB2