PXD059044

PXD059044 is an original dataset announced via ProteomeXchange.

Title	Self-Assembled PROTACs Enable Glycoproteins Degradation in the Living Cells
Description	We report here a two-component proteolysis targeting chimeras (PROTACs) strategy selectively targeting O-GalNAcylated and O-GlcNAcylated proteins for proteasomal degradation, which leads to severe toxicity in human cancer cell lines through perturbation of critical metabolic and signaling pathways governed by glycoproteins. Our approach termed as GlyTACs leverages from metabolic incorporation of easily accessible and cell-permeable peracetylated N-acetylglucosamine (GlcNAc) or N-acetylgalactosamine (GalNAc) analogues bearing an azido group into glycoproteins. In the living cells, the azido-modified glycoproteins serve as a covalent anchor for the introduction of thalidomide moiety by strain-promoted azide-alkyne cycloaddition (SPAAC) to recruit E3 ligase cereblon (CRBN), resulting in stepwise ubiquitination of ‘sensitized’ proteins and their degradation by proteasome. We show the efficiency of the system in a series of human cancer cell lines and verify the mechanistic pathway by performing control experiments at each stage of the process. Given the characteristic features of cancer cells including fast nutrient turnover, and overall increase of protein glycosylation, as well as the low cytotoxicity of the individual components, our approach may open a feasible strategy in cancer therapy.
HostingRepository	PRIDE
AnnounceDate	2025-04-04
AnnouncementXML	Submission_2025-04-04_06:32:09.434.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Pavel Kielkowski
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2024-12-19 05:52:59	ID requested
⏵ 1	2025-04-04 06:32:09	announced

10.1039/D5SC00400D;

submitter keyword: DIA,PROTACs, protein glycosylation

Pavel Kielkowski
contact affiliation	LMU Munich, Department of Chemistry
contact email	pavel.kielkowski@cup.lmu.de
lab head
Pavel Kielkowski
contact affiliation	LMU Munich
contact email	pavel.kielkowski@cup.lmu.de
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/2025/04/PXD059044

PRIDE project URI

• PRIDE
  1. PXD059044
     1. Label: PRIDE project
     2. Name: Self-Assembled PROTACs Enable Glycoproteins Degradation in the Living Cells