PXD040944

PXD040944 is an original dataset announced via ProteomeXchange.

Title	VRK1 regulates sensitivity to oxidative stress by altering the nuclear phosphoproteome and histone epigenetic modifications
Description	Chromatin organization and its dynamic remodeling determine its accessibility and sensitivity to DNA damage. The major source of endogenous DNA damage is oxidative stress. We studied the role of the VRK1 chromatin kinase in the response to oxidative stress, which alters the nuclear phosphoproteome and the histone epigenetic pattern. Oxidative stress causes an accumulation of 8-oxoG DNA lesions that were significantly increased by VRK1 depletion, causing a significant accumulation of DNA strand breaks detected by their labeling with TUNEL assays. The analysis of the nuclear phosphoproteome in response to oxidative stress detected an enrichment of phosphorylated proteins associated with chromosome organization and chromatin remodeling, and these protein phosphorylations significantly decreased after VRK1 depletion. Because chromatin remodeling requires covalent modifications in the histone tails, we studied the effect of oxidative stress on the pattern of histones H4 and H3 epigenetic modifications. Oxidative stress induced the acetylation of H4 in K16, an increase of H3K9 acetylation, and a loss of H3K4me3. Depletion of VRK1 altered all these modifications induced by oxidative stress and resulted in the loss of H4K16ac and H3K9ac and an increase in H3K9me3 and H3K4me3 levels. All these changes induced by oxidative stress in the epigenetic pattern of histones are impaired by the depletion of VRK1, indicating that VRK1 plays a major role in the functional reorganization of chromatin in the response to oxidative stress. VRK1 depletion alters the nuclear phosphoproteome and the histone epigenetic pattern in response to oxidative stress.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:42:43.027.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Thang Pham
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-03-17 07:48:02	ID requested
1	2024-05-24 02:50:33	announced
⏵ 2	2024-10-22 06:42:43	announced	2024-10-22: Updated project metadata.

Navarro-Carrasco E, Monte-Serrano E, Campos-D, í, az A, Rolfs F, de Goeij-de Haas R, Pham TV, Piersma SR, Gonz, á, lez-Alonso P, Jim, é, nez CR, Lazo PA, VRK1 Regulates Sensitivity to Oxidative Stress by Altering Histone Epigenetic Modifications and the Nuclear Phosphoproteome in Tumor Cells. Int J Mol Sci, 25(9):(2024) [pubmed]

10.3390/ijms25094874;

submitter keyword: methylation, acetylation, nuclear proteins,VRK1, oxidative stress, phosphoproteomics, chromatin

Connie Jimenez
contact affiliation	OncoProteomics Laboratory, Amsterdam UMC, The Netherlands
contact email	c.jimenez@amsterdamumc.nl
lab head
Thang Pham
contact affiliation	Amsterdam UMC
contact email	t.pham@amsterdamumc.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD040944
     1. Label: PRIDE project
     2. Name: VRK1 regulates sensitivity to oxidative stress by altering the nuclear phosphoproteome and histone epigenetic modifications