PXD037776

PXD037776 is an original dataset announced via ProteomeXchange.

Title	E4F1 and ZNF148 are transcriptional activators of the A57C and wildtype TERT promoter
Description	Point mutations within the TERT promoter are the most common recurrent somatic non-coding mutation identified across different cancer types, including glioblastoma, melanoma, hepatocellular carcinoma and bladder cancer. They are most abundant at C146T and C124T and more rare at A57C, with the latter originally described as a familial case but subsequently shown also to occur somatically. All three mutations create de novo ETS (E-twenty-six specific) binding sites and result in the reactivation of the TERT gene, allowing cancer cells to achieve replicative immortality. Here, we employed a systematic proteomics screen to identify transcription factors preferentially binding to the C146T, C124T and A57C mutations. While we confirmed binding of multiple ETS factors to the mutant C146T and C124T sequences, we identified E4F1 a an A57C-specific binder and ZNF148 as a TERT WT binder that is excluded from the TERT promoter by the C124T allele. Both proteins are activating transcription factors that bind specifically to the A57C and wildtype (at position 124) TERT promoter sequence in corresponding cell lines and upregulate TERT transcription and telomerase activity.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:13:40.810.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Dennis Kappei
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	6x(13)C; 6x(13)C
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-10-27 03:05:08	ID requested
1	2024-10-07 13:48:29	announced
⏵ 2	2024-10-22 06:13:43	announced	2024-10-22: Updated project metadata.

10.1101/gr.277724.123;

Chua BH, Zaal Anuar N, Ferry L, Domrane C, Wittek A, Mukundan VT, Jha S, Butter F, Tenen DG, Defossez PA, Kappei D, promoter. Genome Res, 33(11):1893-1905(2023) [pubmed]

submitter keyword: TERT promoter mutations, ZNF148, E4F1, telomerase

Dennis Kappei
contact affiliation	Cancer Science Institute of Singapore, National University of Singapore
contact email	dennis.kappei@nus.edu.sg
lab head
Dennis Kappei
contact affiliation	Cancer Science Institute of Singapore
contact email	dennis.kappei@nus.edu.sg
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD037776
     1. Label: PRIDE project
     2. Name: E4F1 and ZNF148 are transcriptional activators of the A57C and wildtype TERT promoter