PXD044931

PXD044931 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2023-08-29 05:14:29	ID requested
⏵ 1	2025-05-07 05:24:02	announced

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]

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)

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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/05/PXD044931

PRIDE project URI

• PRIDE
  1. PXD044931
     1. Label: PRIDE project
     2. Name: TIPRL1 and its ATM-dependent phosphorylation modulate the DNA Damage Response to promote radiotherapy resistance in head and neck cancer