Phospho-proteomics analysis of early-response to x-ray irradiation reveals molecular mechanisms potentially related to U251 cells radioresistance

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Diouf, Ousseynou Ben | Gilbert, Antoine | Bernay, Benoit | Soumboundou, Mamadou | M’kacher, Radhia | Sall, Cheikh | Chevalier, François

Edité par CCSD -

International audience. Glioblastoma (GBM) is a devastating malignant brain tumor with a poor prognosis. GBM is associated with radioresistance to X-rays. The most crucial intrinsic primary factors of GBM radioresistance remain the response to DNA damage, survival and cell proliferation. To better understand the biological mechanisms involved in GBM radioresistance, we carried out a phospho-proteomic study on U251 cell line, 3H after X-ray irradiation (6 Gy) and on non-irradiated cells. Direct mass spectrometry analysis showed 453 phospho-peptides differentially expressed (DEPs) with 211 overexpressed and 242 downexpressed in our two conditions. After Gene Ontology (GO) enrichment, results showed a strong upregulation of BRCA1-B complex affected by overexpression of BRCA1 phospho-peptide. At the same time, a downregulation of cell cycle processes and the cell cycle itself was associated with downexpressed phospho-peptides ANLN, TPR, TOP2B. Our results revealed increased diversity of the phospho-proteome defined by DNA damage and biological mechanisms involved the early response of GBM cell to irradiation potentially linked to GBM radioresistance.

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