PXD056951-1

PXD056951 is an original dataset announced via ProteomeXchange.

Title	Whole cell proteome of HeLa Flp in T-RexTM RNF4 WT treated with either CCW16, 1a or 2c
Description	The SUMO-targeted E3 ubiquitin ligase RNF4 plays an important role in safeguarding genome and proteome integrity. RNF4 recognizes polySUMO modified proteins and induces their proteolytic or non-proteolytic ubiquitylation. Based on the key functions of RNF4 maintaining proteome and genome stability, control of DNA damage response and DNA-protein crosslink repair, we explored its role in cancer cell survival and as a potential drug target. We found that RNF4 is overexpressed in acute myeloid leukemia and expression levels correlate with poor survival. To develop PROTACs for targeted degradation of RNF4, we aimed to exploit the recently developed cysteine-reactive RNF4 ligand CCW16, and synthesized a set of CCW16-derived degrader molecules using established VHL- and CRBN E3 ligands. We showed that treatment with two CCW16-derived PROTACs leads to overexpression of HMOX1, a ferroptosis marker, and HSP70 protein family members. However, we could not detect a significant reduction of RNF4 levels. Interestingly, also the RNF4 binder CCW16 itself induced the expression of HMOX1. Altogether our data indicates that treatment with CCW16 leads to a ferroptotic cell death pathway.
HostingRepository	PRIDE
AnnounceDate	2025-10-13
AnnouncementXML	Submission_2025-10-13_03:58:43.946.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Stefan Müller
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-18 07:28:56	ID requested
⏵ 1	2025-10-13 03:58:44	announced

10.1038/S44319-025-00593-4;

submitter keyword: RNF4, TMT,WCP, CCW16, mammalian cells

Prof. Dr. Stefan Müller
contact affiliation	Institute of Biochemistry II, Goethe University Frankfurt,Medical Faculty, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
contact email	ste.mueller@em.uni-frankfurt.de
lab head
Stefan Müller
contact affiliation	Institute of Biochemistry II University Hospital Building 75 Theodor-Stern-Kai 7 60590 Frankfurt (Main)
contact email	ag-mueller@gmx.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/2025/10/PXD056951

PRIDE project URI

• PRIDE
  1. PXD056951
     1. Label: PRIDE project
     2. Name: Whole cell proteome of HeLa Flp in T-RexTM RNF4 WT treated with either CCW16, 1a or 2c