PXD067752

PXD067752 is an original dataset announced via ProteomeXchange.

Title	The protein kinase DYRK1B is a p53 target gene and functions as a negative feedback regulator of the transcription factor RFX7 - Proteome
Description	The tumor suppressor protein p53 orchestrates cellular responses to stress by regulating the transcription of target genes involved in processes such as cell cycle control, DNA damage repair and apoptosis. The protein kinase DYRK1B, known to promote cancer cell survival and contribute to DNA damage repair, is overexpressed in various tumor types. Here, we demonstrate that expression of DYRK1B - but not its closely related paralog DYRK1A - is upregulated by cytostatic drugs (Actinomycin D, Doxorubicin) in multiple cancer cell lines. This induction required functional p53 and was mediated by p53-dependent activation of the transcription factor RFX7. Furthermore, we show that DYRK1B physically interacts with RFX7 and counteracts its activation by p53, thereby establishing a negative feedback loop that attenuates RFX7- dependent gene expression. This inhibitory effect of DYRK1B was strictly dependent on its catalytic activity and could be blocked by using small-molecule DYRK1 inhibitors. In conclusion, our study identifies DYRK1B as an indirect p53 target that suppresses p53- mediated activation of RFX7. These findings suggest that pharmacological inhibition of DYRK1B may represent a therapeutic strategy to enhance RFX7 tumor suppressor function.
HostingRepository	PRIDE
AnnounceDate	2026-03-31
AnnouncementXML	Submission_2026-03-31_11:05:28.831.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sebastian Kallabis
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	phosphorylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-08-26 10:21:47	ID requested
⏵ 1	2026-03-31 11:05:29	announced

10.1038/S41419-026-08660-X;

submitter keyword: DYRK1B,DYRK1A, A549, RFX7, p53

Walter Becker
contact affiliation	Institute of Pharmacology and Toxicology, RWTH Aachen University, 52074 Aachen, Germany;
contact email	wbecker@ukaachen.de
lab head
Sebastian Kallabis
contact affiliation	Core Facility Translational Proteomics Medical Faculty University Bonn Venusberg - Campus 1 53127 Bonn Germany
contact email	kallabis@uni-bonn.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD067752
     1. Label: PRIDE project
     2. Name: The protein kinase DYRK1B is a p53 target gene and functions as a negative feedback regulator of the transcription factor RFX7 - Proteome