PXD060120

PXD060120 is an original dataset announced via ProteomeXchange.

Title	Graded levels of p53 activation modulate endothelial cell fate and specification during angiogenesis
Description	The cell cycle is a key regulator of endothelial cell specification into tip and stalk cell phenotypes, which are essential for angiogenesis in both normal development and pathological conditions. While the tumor suppressor p53 is known to regulate the cell cycle and influence cell fate, its role in the specification of endothelial cell phenotypes remains unclear. Using non-genotoxic small molecule and stapled peptide compounds to activate p53, we demonstrate that graded levels of p53 activation induce distinct cellular fates in normal endothelial cells. Low levels of p53 activation induce reversible cell cycle arrest by reducing DNA replication, while high levels induce senescence and cell death through disruptions in ribosome assembly. Surprisingly, all tested levels of p53 activation reduced the growth of venous blood vessels in vitro and in zebrafish embryo models. This reduction likely stems from distinct cellular responses in tip and stalk cells in response to p53 activation: low p53 levels primarily impaired stalk cell proliferation and elongation, whereas high levels impaired both tip and stalk cell specification. Our findings show for the first time that graded levels of p53 modulate endothelial cell fate and specification, providing new insights into the ways in which p53 regulates angiogenesis. These findings highlight the potential of using p53 modulation as a therapeutic strategy to target abnormal tip or stalk cell specification in vascular diseases, such as cancer.
HostingRepository	PRIDE
AnnounceDate	2025-12-22
AnnouncementXML	Submission_2025-12-21_16:07:51.204.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Akos Vegvari
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-01-23 09:28:52	ID requested
⏵ 1	2025-12-21 16:07:52	announced

10.1038/s41419-025-08292-7;

Al-Radi O, Ingelshed K, Eichhorn L, Josefsson H, Krkoska M, Br, ä, utigam L, Lindstr, ö, m S, V, é, gv, á, ri Á, Kheder S, Cerrato CP, Ferm, é S, Bosdotter C, Allalou A, Levander F, Vojtesek B, Lane DP, Kannan P, Pharmacological activation of p53 induces dose-dependent changes in endothelial cell fate during angiogenic sprouting. Cell Death Dis, 16(1):883(2025) [pubmed]

submitter keyword: angiogenesis,p53

Akos Vegvari
contact affiliation	Karolinska Institutet, Stockholm, Sweden
contact email	akos.vegvari@ki.se
lab head
Akos Vegvari
contact affiliation	Karolinska Institutet
contact email	akos.vegvari@ki.se
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD060120
     1. Label: PRIDE project
     2. Name: Graded levels of p53 activation modulate endothelial cell fate and specification during angiogenesis