PXD066365-1

PXD066365 is an original dataset announced via ProteomeXchange.

Title	DCAF1 interacting partners in myeloma cells
Description	Multiple myeloma is a plasma cell malignancy that is susceptible to drugs targeting protein homeostasis such as thalidomide analogues and proteasome inhibitors. Thalidomide analogues modulate the activity of DDB1/CUL4 E3-ligase complexes to perturb substrate recognition and proteasomal degradation thereof. We hypothesised that the cellular pool of DDB1/CUL4 associated factors (DCAFs) may mediate other essential plasma cell processes and offer new targets for therapeutic intervention. Unbiased genetic screening identified DCAF1 (also known as Vpr-binding protein; VPRBP) as essential for myeloma cell survival with a multidomain structure offering several distinct opportunities for drug development. Utilising B32B3, a previously disclosed DCAF1 kinase inhibitor as a template, we developed a series of analogues with enhanced anti-myeloma potency. As anti-myeloma activity did not associate with dephosphorylation of known DCAF1 kinase substrates, we correlated drug-induced cellular phenotypes with whole-genome CRISPR/Cas9 resistance screening to further define mechanistic activity. These studies identified B32B3 analogues as microtubular destabilising agents with potential DCAF1 kinase independent properties and in vivo efficacy in multiple myeloma and lymphoma.
HostingRepository	PRIDE
AnnounceDate	2025-10-06
AnnouncementXML	Submission_2025-10-05_20:46:20.779.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Laura Dagley
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-21 07:33:16	ID requested
⏵ 1	2025-10-05 20:46:21	announced

Dataset with its publication pending

submitter keyword: Human JJN3 myeloma cells

DCAF1/VPRBP

Associate Professor Lev Kats
contact affiliation	Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
contact email	lev.kats@petermac.org
lab head
Laura Dagley
contact affiliation	WEHI
contact email	dagley.l@wehi.edu.au
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD066365
     1. Label: PRIDE project
     2. Name: DCAF1 interacting partners in myeloma cells