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PXD011925

PXD011925 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleA proteomics-based interaction screen links DYRK1A to RNF169 and to the DNA damage response
DescriptionDYRK1A 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.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_04:57:35.705.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterEva Borràs
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue
InstrumentLTQ Orbitrap Velos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02018-12-03 08:26:19ID requested
12019-06-18 03:31:12announced
22019-07-12 02:58:53announcedUpdated publication reference for PubMed record(s): 30979931, 31208443.
32024-10-22 04:57:37announced2024-10-22: Updated project metadata.
Publication List
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]
Keyword List
curator keyword: Biological
submitter keyword: DYRK1A, RNF169, DNA damage, interactome, LCMSMS
Contact List
Eduard Sabido
contact affiliationCenter for Genomic Regulation and University Pompeu Fabra
contact emaileduard.sabido@crg.eu
lab head
Eva Borràs
contact affiliationUPF
contact emaileva.borras@upf.edu
dataset submitter
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Dataset FTP location
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