PXD035010 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
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. |
Publication List
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] |
Keyword List
submitter keyword: ADAM |
Adaptive response |
ALK1 |
ALK5 |
Bystander effects |
Hyper-radiosensi-27 tive response |
Low-dose radiation |
Low dose rate |
MMP |
TGF-β3 |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD035010
- Label: PRIDE project
- 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