PXD064507-1

PXD064507 is an original dataset announced via ProteomeXchange.

Title	A Chemogenetic CRISPR Knock-out Screen Uncovers Synergy Between Ubiquitin Signalling and C16orf72/HAPSTR1 for safeguarding S phase integrity
Description	Cell cycle progression is orchestrated by a 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 TAK-243. Our findings provide a systems view of key protein networks underpinning cell cycle progression. We identified 239 genes, including C16orf72/HAPSTR1, whose ablation rendered cells sensitive to a ubiquitin signalling blockade, and 55 genes that conferred resistance under the same conditions. We reveal broad transcriptional changes accompanied with proteome-wide alterations in the ubiquitin signalling landscape upon loss of HAPSTR1 expression, revealing that HAPSTR1 is involved in homeostasis of cell cycle regulators such as CDK6 and CDC6. Mechanistically, we found that HAPSTR1 orchestrates the timing of the G1/S-transition via RB-E2F1 pathway activation by CDK6. Under diminished ubiquitin signalling, compensatory mechanisms fail to respond to accelerated S phase entry and replication stress upon loss of HAPSTR1, eventually compromising cell cycle integrity. Altogether, we provide a valuable resource on the interplay between the ubiquitin system and cell proliferation and uncover HAPSTR1 as a transcriptional regulator orchestrating the G1/S transition.
HostingRepository	PRIDE
AnnounceDate	2026-09-04
AnnouncementXML	Submission_2026-09-04_06:15:58.559.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Rayman Tjokrodirijo
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Astral

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-02 04:41:53	ID requested
⏵ 1	2026-09-04 06:15:59	announced

Dataset with its publication pending

submitter keyword: Cell cycle, HAPSTR1, S phase, CDK6, ubiquitin signalling

Peter A. van Veelen
contact affiliation	Head Proteomics Group, Leiden University Medical Center, Center for Proteomics and Metabolomics, PO Box 9600, Postal zone P1-Q, 2300 RC Leiden, The Netherlands
contact email	P.A.van_Veelen@lumc.nl
lab head
Rayman Tjokrodirijo
contact affiliation	Leiden University Medical Center, Proteomics group
contact email	r.t.n.tjokrodirijo@lumc.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD064507
     1. Label: PRIDE project
     2. Name: A Chemogenetic CRISPR Knock-out Screen Uncovers Synergy Between Ubiquitin Signalling and C16orf72/HAPSTR1 for safeguarding S phase integrity