PXD078382

PXD078382 is an original dataset announced via ProteomeXchange.

Title	Druggable linker histone variant H1-10 promotes ribosome biogenesis and nucleolar assembly in prostate cancer
Description	Linker histone H1 stabilizes chromatin, but the functions of its variants remain incompletely understood. Among the seven somatic H1 variants, H1-10 has the minimal sequence similarity to others, suggesting a distinct biological role. Here, we show that H1-10, unlike other somatic variants, localizes predominantly to the nucleolus, where it promotes nucleolar assembly through liquid-liquid phase condensation and enhances RNA polymerase I occupancy at ribosomal DNA (rDNA). This results in amplified rRNA transcription and increased global protein synthesis. H1-10 is upregulated across multiple cancer types and, in prostate cancer, selectively augments E2F3 translation, thereby activating a broad cell-growth transcriptional program. Through structure-based screening, we identified first-in-class small-molecule inhibitors that disrupt H1-10 DNA binding and nucleolar localization, effectively suppressing prostate tumor growth without overt toxicity. Lead optimization produced compound CN27 (IC₅₀ = 180 nM; >100-fold selectivity of H1-10 over H1-1/H1-6), which demonstrated potent efficacy in castration-resistant prostate cancer models. Collectively, our findings uncover a critical role of H1-10 in ribosome biogenesis and oncogenic translation, providing proof-of-concept for pharmacological targeting of histone variants.
HostingRepository	PRIDE
AnnounceDate	2026-05-18
AnnouncementXML	Submission_2026-05-18_09:06:38.466.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Wenzheng Wang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2026-05-15 00:26:37	ID requested
⏵ 1	2026-05-18 09:06:38	announced

Dataset with its publication pending

ProteomeXchange project tag: Cancer (B/D-HPP), Biology/Disease-Driven Human Proteome Project (B/D-HPP), Human Proteome Project

submitter keyword: prostate cancer, Linker histone H1-10, LC-MS/MS

Haiyang Guo
contact affiliation	Shandong University
contact email	haiyang.guo@email.sdu.edu.cn
lab head
Wenzheng Wang
contact affiliation	Shandong University
contact email	wwz12_cpu@163.com
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/2026/05/PXD078382

PRIDE project URI

• PRIDE
  1. PXD078382
     1. Label: PRIDE project
     2. Name: Druggable linker histone variant H1-10 promotes ribosome biogenesis and nucleolar assembly in prostate cancer