PXD035010

PXD035010 is an original dataset announced via ProteomeXchange.

Title	Low dose rate radiation induced secretion of TGF-β3 together 2 with an activator in small extracellular vesicles modifies low 3 dose hyper-radiosensitivity through ALK1 binding
Description	Hyper-radiosensitivity (HRS) is the increased sensitivity to low doses of ionizing radiation 12 observed in most cell lines. We previously demonstrated that HRS is permanently abolished in cells irradiated at a low dose rate (LDR), in a mechanism dependent on transforming growth factor β3 (TGF-β3). In this study, we aimed to elucidate the activation and receptor binding of TGF-β3 in this mechanism. T-47D cells were pre-treated with inhibitors of potential receptors and activators of TGF-β3, along with addition of small extracellular vesicles (sEVs) from LDR primed cells, before their radiosensitivity was assessed by the clonogenic assay. The protein content of sEVs from LDR primed cells was analyzed with mass spectrometry. Our results show that sEVs contain TGF-β3 regardless of priming status, but only sEVs from LDR primed cells remove HRS in reporter cells. Inhibition of the matrix metalloproteinase (MMP) family prevents removal of HRS, suggesting an MMP-dependent activation of TGF-β3 in the LDR primed cells. We demonstrate a functional interaction between TGF-β3 and activin receptor like kinase 1 (ALK1), by showing that TGF-β3 removes HRS through ALK1 binding, independent of ALK5 and TGF-βRII. These results are an important contribution to a more comprehensive understanding of the mechanism behind TGF-β3 mediated removal of HRS.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:38:58.141.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD035010
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Bernd Thiede
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	S-carboxamidoethyl-L-cysteine; monohydroxylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2022-06-30 03:29:15	ID requested
1	2022-08-11 20:59:05	announced
⏵ 2	2024-10-22 05:38:59	announced	2024-10-22: Updated project metadata.

10.6019/PXD035010;

10.3390/ijms23158147;

Hanson I, Pitman KE, Altanerova U, Altaner Č, Malinen E, Edin NFJ, 3 Together with an Activator in Small Extracellular Vesicles Modifies Low-Dose Hyper-Radiosensitivity through ALK1 Binding. Int J Mol Sci, 23(15):(2022) [pubmed]

submitter keyword: ADAM

Adaptive response

ALK1

ALK5

Bystander effects

Hyper-radiosensi-27 tive response

Low-dose radiation

Low dose rate

MMP

TGF-β3

Ingunn Hanson
contact affiliation	University of Oslo, Department of Physics
contact email	Ingunn.Hanson@fys.uio.no
lab head
Bernd Thiede
contact affiliation	University of Oslo
contact email	bernd.thiede@ibv.uio.no
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD035010
     1. Label: PRIDE project
     2. Name: Low dose rate radiation induced secretion of TGF-β3 together 2 with an activator in small extracellular vesicles modifies low 3 dose hyper-radiosensitivity through ALK1 binding