PXD065780-1

PXD065780 is an original dataset announced via ProteomeXchange.

Title	Activation of the HPV16 late promoter by viral E2 and cellular BRD4 and ZC3H4 proteins
Description	High-risk human papillomaviruses (HPV), particularly HPV16, are major causes of anogenital and oropharyngeal cancers. The HPV late promoter, P670 in the case of HPV16, is activated upon host cell differentiation and drives expression of viral capsid proteins. While differentiation-specific host transcription factors have been implicated in regulating this promoter, the mechanism remains incompletely understood. HPV E2 proteins activate transcription by interacting with the host protein BRD4 (Bromodomain-containing protein 4). A biotin proximity ligation screen identified several novel E2 interactors, of which many overlap with the BRD4 interactome, suggesting BRD4 mediates a large fraction of these interactions. One such interactor, ZC3H4 (Zinc finger CCCH domain-containing protein 4), is known to restrict the expression of long non-coding RNAs, including enhancer and promoter upstream antisense (ua) RNAs. E2 recruits ZC3H4 in a BRD4-dependent manner to specifically activate the P670 promoter in reporter assays. Supporting this, E2 and ZC3H4 co-localize in cells with high P670 activity. ZC3H4 is upregulated during differentiation, and its knockdown in differentiated HPV16- or HPV31-positive cells reduces late viral transcripts in an E2-BRD4-dependent manner. Interestingly, knockdown of ZC3H4 also increases cellular, but not viral, uaRNAs, suggesting that ZC3H4 enhances HPV late transcription through a previously unrecognized mechanism.
HostingRepository	MassIVE
AnnounceDate	2025-07-04
AnnouncementXML	Submission_2025-07-04_03:18:11.038.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Karsten Boldt
SpeciesList	scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; scientific name: Human papillomavirus; NCBI TaxID: 10566;
ModificationList	CarbamidomethylDTT; Acetyl; Oxidation
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-04 02:31:11	ID requested
⏵ 1	2025-07-04 03:18:11	announced

no publication

submitter keyword: BioID, HPV, LFQ, DatasetType:Proteomics

Karsten Boldt
contact affiliation	Eberhard-Karls Universitaet Tuebingen
contact email	karsten.boldt@uni-tuebingen.de
lab head
Karsten Boldt
contact affiliation	Eberhard-Karls Universit?t T?bingen
contact email	karsten.boldt@uni-tuebingen.de
dataset submitter

MassIVE dataset URI

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