PXD037776 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
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. |
Publication List
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] |
Keyword List
submitter keyword: TERT promoter mutations, ZNF148, E4F1, telomerase |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD037776
- Label: PRIDE project
- Name: E4F1 and ZNF148 are transcriptional activators of the A57C and wildtype TERT promoter