PXD044931 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | TIPRL1 and its ATM-dependent phosphorylation modulate the DNA Damage Response to promote radiotherapy resistance in head and neck cancer |
Description | TIPRL1 (target of rapamycin signaling pathway regulator-like 1) is a known interactor and inhibitor of protein phosphatases PP2A, PP4 and PP6 – all pleiotropic modulators of the DNA Damage Response (DDR). Here, we describe a new role for TIPRL1 in the radiotherapy (RT) response of Head and Neck Squamous Cell Carcinoma (HNSCC). TIPRL1 expression was found increased in tumor versus non-tumor tissue, with high tumoral TIPRL1 expression associating with lower locoregional control and decreased survival of RT-treated patients. TIPRL1 deletion in SQD9 cells resulted in increased RT sensitivity, a faster cell cycle arrest, increased micronuclei formation and an altered proteome-wide DDR. Upon irradiation, ATM phosphorylates TIPRL1 at Ser265, contributing to TIPRL1-mediated RT resistance. Mass spectrometry analysis identified DNA-PKcs, RAD51 and nucleosomal histones as novel TIPRL1 interactors in irradiated cells. Histone binding, although stimulated by RT, was adversely affected by TIPRL1 Ser265 phosphorylation. Our findings underscore a clinically relevant role for TIPRL1 and its ATM-dependent phosphorylation in RT resistance through modulation of DNA damage checkpoint activation and repair. |
HostingRepository | PRIDE |
AnnounceDate | 2025-05-07 |
AnnouncementXML | Submission_2025-05-07_05:24:02.063.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD044931 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | Rita Derua |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-08-29 05:14:29 | ID requested | |
⏵ 1 | 2025-05-07 05:24:02 | announced | |
Publication List
10.6019/PXD044931; |
10.1007/s13402-023-00895-6; |
Cokelaere C, Dok R, Cortesi EE, Zhao P, Sablina A, Nuyts S, Derua R, Janssens V, TIPRL1 and its ATM-dependent phosphorylation promote radiotherapy resistance in head and neck cancer. Cell Oncol (Dordr), 47(3):793-818(2024) [pubmed] |
Keyword List
submitter keyword: Ataxia Telangiectasia Mutated (ATM) kinase/ DNA Damage Response (DDR)/ Head and Neck Squamous Cell Carcinoma (HNSCC)/ radioresistance/ target of rapamycin signaling pathway regulator-like 1 (TIPRL1) |
Contact List
Prof. Dr. Veerle Janssens |
contact affiliation | Department Cellular and Molecular Medicine KU Leuven Belgium |
contact email | veerle.janssens@kuleuven.be |
lab head | |
Rita Derua |
contact affiliation | KU Leuven |
contact email | rita.derua@kuleuven.be |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD044931
- Label: PRIDE project
- Name: TIPRL1 and its ATM-dependent phosphorylation modulate the DNA Damage Response to promote radiotherapy resistance in head and neck cancer