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PXD044931

PXD044931 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleTIPRL1 and its ATM-dependent phosphorylation modulate the DNA Damage Response to promote radiotherapy resistance in head and neck cancer
DescriptionTIPRL1 (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.
HostingRepositoryPRIDE
AnnounceDate2025-05-07
AnnouncementXMLSubmission_2025-05-07_05:24:02.063.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD044931
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterRita Derua
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-08-29 05:14:29ID requested
12025-05-07 05:24:02announced
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 affiliationDepartment Cellular and Molecular Medicine KU Leuven Belgium
contact emailveerle.janssens@kuleuven.be
lab head
Rita Derua
contact affiliationKU Leuven
contact emailrita.derua@kuleuven.be
dataset submitter
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Dataset FTP location
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