PXD011925

PXD011925 is an original dataset announced via ProteomeXchange.

Title	A proteomics-based interaction screen links DYRK1A to RNF169 and to the DNA damage response
Description	DYRK1A is a protein kinase whose dysregulation is linked to disease in humans. On the one side, its overexpression in trisomy 21 has been linked to certain Down syndrome pathological traits, while inactivating mutations in just one allele that hinders its function are responsible for a rare clinical syndrome. Moreover, altered expression of this kinase could be at the basis of other human pathologies including cancer and diabetes. Although, a few DYRK1A substrates have been described there is still a poor knowledge on both upstream regulators and downstream targets that could explain DYRK1A cellular activities. Where, we carried out a proteomics screen using antibody-based affinity purification coupled to mass spectrometry to identify cellular proteins that bind directly or indirectly to endogenous DYRK1A. We show that the use of a cell line not expressing DYRK1A, generated by CRISPR/Cas9 technology, was needed to discriminate between true positives and non-specific interactors. Most of the proteins found in the screen are novel DYRK1A interactor candidates, which are linked to a variety of cellular functions. The in-depth characterization of the functional interaction with one of them, the E3 ubiquitin ligase RNF169, has revealed a role forfor the link of DYRK1A inwith the DNA damage response. We found that RNF169 is a DYRK1A substrate and identified several phosphositesof its phosphorylation sites. In particular, one of the sites appears to contribute to the ability of RNF169 to displaced 53BP1 from sites of DNA damage at chromatin. Additionally, depletion of DYRK1A increases cell sensitivity to DNA damage. Therefore, our unbiased proteomic screen has revealed a novel functional activity for DYRK1A expanding the complex role of this kinase in controlling cellular homeostasis.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:57:35.705.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Eva Borràs
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2018-12-03 08:26:19	ID requested
1	2019-06-18 03:31:12	announced
2	2019-07-12 02:58:53	announced	Updated publication reference for PubMed record(s): 30979931, 31208443.
⏵ 3	2024-10-22 04:57:37	announced	2024-10-22: Updated project metadata.

10.1038/s41598-019-42445-x;

Roewenstrunk J, Di Vona C, Chen J, Borras E, Dong C, Arat, ó K, Sabid, ó E, Huen MSY, de la Luna S, A comprehensive proteomics-based interaction screen that links DYRK1A to RNF169 and to the DNA damage response. Sci Rep, 9(1):6014(2019) [pubmed]

curator keyword: Biological

submitter keyword: DYRK1A, RNF169, DNA damage, interactome, LCMSMS

Eduard Sabido
contact affiliation	Center for Genomic Regulation and University Pompeu Fabra
contact email	eduard.sabido@crg.eu
lab head
Eva Borràs
contact affiliation	UPF
contact email	eva.borras@upf.edu
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/2019/07/PXD011925

PRIDE project URI

• PRIDE
  1. PXD011925
     1. Label: PRIDE project
     2. Name: A proteomics-based interaction screen links DYRK1A to RNF169 and to the DNA damage response