PXD050046-1

PXD050046 is an original dataset announced via ProteomeXchange.

Title	A Chemogenetic CRISPR Knock-out Screen Uncovers Synergy Between Ubiquitin Signaling and C16orf72/HAPSTR1 for S-phase Entry
Description	Cell cycle progression is orchestrated by complex interplay between post-translational modifications (PTMs) controlling activation (phosphorylation) and degradation (ubiquitination) of key cell cycle regulators. To comprehensively identify ubiquitin signalling components critical for cell proliferation, we employed a chemical-genetic CRISPR knock-out screen exploiting the first-in-class ubiquitin E1 inhibitor TAK243. We identified 239 genes, including C16orf72/HAPSTR1, whose mutation rendered cells sensitive and 55 genes conferring resistance to diminished ubiquitin signaling, providing a systems view of key protein networks underpinning cell cycle progression. Proteome-wide alterations in the ubiquitin signaling landscape as a function of HAPSTR1 expression, revealed increased ubiquitination of the cell cycle regulator CDK6. Mechanistically, we find that HAPSTR1 controls the timing of S-phase entry via RB-E2F1 pathway activation by CDK6. Strikingly, the HAPSTR1/CDK6 axis is finetuned by the ubiquitin proteasome system (UPS), enforcing cell cycle-dependent turnover of both proteins. Although CDKs have long been thought of as stable elements of the cell cycle machinery, this conventional notion is challenged by our present findings, demonstrating UPS-dependent fluctuations in CDK6 expression. Altogether, we provide a valuable resource on the interplay between the ubiquitin system and cell proliferation and uncover HAPSTR1 as a regulator of CDK6 levels to orchestrate G1/S transition.
HostingRepository	PRIDE
AnnounceDate	2026-09-07
AnnouncementXML	Submission_2026-09-07_14:30:28.070.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Vyacheslav Akimov
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	ubiquitination signature dipeptidyl lysine
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-02-22 15:03:47	ID requested
⏵ 1	2026-09-07 14:30:28	announced

Dataset with its publication pending

submitter keyword: DIA-MS, PTM,Cell cycle, ubiquitination

Dr. Blagoy Blagoev
contact affiliation	Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark
contact email	bab@bmb.sdu.dk
lab head
Vyacheslav Akimov
contact affiliation	Center for Experimental BioInformatics, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark
contact email	akimov@bmb.sdu.dk
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/2026/09/PXD050046

PRIDE project URI

• PRIDE
  1. PXD050046
     1. Label: PRIDE project
     2. Name: A Chemogenetic CRISPR Knock-out Screen Uncovers Synergy Between Ubiquitin Signaling and C16orf72/HAPSTR1 for S-phase Entry