PXD019589

PXD019589 is an original dataset announced via ProteomeXchange.

Title	Temporal modulation of the NF-kB network in response to different types of DNA damage HYDROXYUREA C4PR_LIV
Description	Different types of DNA damage can initiate phosphorylation-mediated signalling cascades that result in stimulus specific pro- or anti-apoptotic cellular responses. Amongst its many roles, the NF-κB transcription factor RelA is central to the DNA damage response pathway. Yet, understanding of the co-ordinated signalling mechanisms that result in these different DNA damaging agents inducing specific cellular outcomes through RelA remains unclear. Here, we examine the temporal effects of exposure of U2OS cells to either etoposide (ETO) or hydroxyurea (HU) on the phosphorylation status of RelA and its protein binding partners, using label-free quantitative phosphoproteomics. Although there were relatively few stimulus specific differences overall in the phosphorylated RelA interactome in response to either DNA damaging agent, we observed subtle, but significant changes in the phosphorylation states of the RelA bound proteins as a function of both the type of and duration of the DNA damaging agent used. The DNA double strand break (DSB) inducing ETO invoked more rapid, sustained responses than HU, with regulated targets primarily involved in transcription, cell division and (unsurprisingly) DSB repair. Kinase substrate prediction of confident, differentially regulated phosphosites suggests possible roles for CDK1 and MAPK3/ERK1 signaling, in addition to the known roles of ATM/ATR. In contrast, HU-induced replicative stress mediated more temporally dynamic regulation, with phosphoprotein components of the RelA network having known roles in rRNA/mRNA processing and translational initiation, many of which contained a 14-3-3ε binding motif. Our data thus point to differential regulation of key cellular processes and the involvement of unique signalling pathways in modulating DNA damage-specific functions of RelA.
HostingRepository	PRIDE
AnnounceDate	2021-09-09
AnnouncementXML	Submission_2021-09-09_02:24:46.906.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Catarina Franco
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2020-06-04 06:57:15	ID requested
⏵ 1	2021-09-09 02:24:47	announced

Campbell AE, Ferraz Franco C, Su LI, Corbin EK, Perkins S, Kalyuzhnyy A, Jones AR, Brownridge PJ, Perkins ND, Eyers CE, B RelA network in response to different types of DNA damage. Biochem J, 478(3):533-551(2021) [pubmed]

submitter keyword: DNA damage

RelA

p65

NF-κB

phosphorylation

Mass Spectrometry, phosphoproteomics

etoposide

hydroxyurea

Claire Eyers
contact affiliation	Director, Centre for Proteome Research Department of Biochemistry & Systems Biology Institute of Systems, Molecular & Integrative Biology University of Liverpool Crown Street, Liverpool L69 7ZB +44 151 795 4424
contact email	ceyers@liverpool.ac.uk
lab head
Catarina Franco
contact affiliation	Centre for Proteome Research, University of Liverpool
contact email	catarina.franco@liverpool.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD019589
     1. Label: PRIDE project
     2. Name: Temporal modulation of the NF-kB network in response to different types of DNA damage HYDROXYUREA C4PR_LIV