PXD074414

PXD074414 is an original dataset announced via ProteomeXchange.

Title	Targeted protein degradation of the CPSF complex by benzoxaboroles through sumoylation
Description	Benzoxaboroles (BoBs) feature a boron-heterocyclic core and are an important innovation in the development of drugs against a range of pathogens and other pathologies. A broad spectrum of pharmacology is associated with chemically diverse BoB derivatives and includes multiple modes-of-action (MoA) and targets. However, a consensus MoA for BoBs targeting evolutionarily diverse protozoan pathogens has emerged with the identification of CPSF3/CPSF73 in the CPSF complex in both apicomplexan and kinetoplastida parasites. Here we establish a functional connection between protein sumoylation and the boron-heterocyclic scaffold shared by all BoBs using comprehensive genetic screens in Trypanosoma brucei. There is a rapid temporal and spatial shift in global protein sumoylation following BoB exposure and members of the CPSF complex are specifically destabilised in a SUMO and proteosome-dependent manner. Finally, we find rapid decrease in bulk mRNA levels, consistent with the role of CPSF3 in mRNA maturation. We propose that a combination of direct inhibition coupled with targeted degradation of CPSF3 underpins the specificity of BoBs against trypanosomatids.
HostingRepository	PRIDE
AnnounceDate	2026-02-13
AnnouncementXML	Submission_2026-02-12_16:41:41.993.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Michele Tinti
SpeciesList	scientific name: Trypanosoma brucei; NCBI TaxID: NEWT:5691;
ModificationList	carbamoylated residue
Instrument	Orbitrap Astral

Revision	Datetime	Status	ChangeLog Entry
0	2026-02-12 15:53:02	ID requested
⏵ 1	2026-02-12 16:41:42	announced

Dataset with its publication pending

submitter keyword: CPSF benzoxaboroles sumoylation

David Horn
contact affiliation	Professor
contact email	d.horn@dundee.ac.uk
lab head
Michele Tinti
contact affiliation	Dundee University
contact email	m.tinti@dundee.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD074414
     1. Label: PRIDE project
     2. Name: Targeted protein degradation of the CPSF complex by benzoxaboroles through sumoylation