PXD049697-1

PXD049697 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	2026-09-01
AnnouncementXML	Submission_2026-09-01_03:52:52.854.xml
DigitalObjectIdentifier	https://doi.org/10.6019/PXD049697
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Nila Overbeek
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-02-19 11:34:35	ID requested
⏵ 1	2026-09-01 03:52:53	announced
2	2026-09-01 03:54:25	announced	2026-09-01: Updated project metadata.

10.6019/PXD049697;

submitter keyword: Ubiquitin, C16orf72, TAK243, HAPSTR1, cell cycle, HUWE1

Alfred C. O. Vertegaal
contact affiliation	Cell & Chemical Biology LUMC Leiden The Netherlands
contact email	a.c.o.vertegaal@lumc.nl
lab head
Nila Overbeek
contact affiliation	LUMC
contact email	n.k.van_overbeek@lumc.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD049697
     1. Label: PRIDE project
     2. Name: A Chemogenetic CRISPR Knock-out Screen Uncovers Synergy Between Ubiquitin Signaling and C16orf72/HAPSTR1 for S-phase Entry.